bluuebunny/crossref_metadata_2025_split huggingface dataset:
Darvadstrocel for Complex Perianal Fistulas in Japanese Adults with Crohn’s Disease: A Phase 3 Study
Authors: Furukawa Satomi , Mizushima Tsunekazu , Nakaya Ryo , Shibata Mari , Yamaguchi Takayoshi , Watanabe Kenji , Futami Kitaro 
Published: September 2022

AbstractBackground and AimsPrevious studies conducted in Europe suggested that darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn’s disease. The aim of this study was to evaluate the efficacy and safety of darvadstrocel for the treatment of complex perianal fistulas in Japanese adults with Crohn’s disease.MethodsThis is a phase 3, open-label, single-arm study conducted at nine sites in Japan. Adult patients with non-active or mildly active Crohn’s disease and complex perianal fistulas received a single 24-mL intralesional injection of darvadstrocel [120 × 106 cells]. The primary endpoint was combined remission (clinically confirmed closure of all treated external openings that were draining at screening, and absence of collections &gt;2 cm, [confirmed by magnetic resonance imaging] among treated fistulas) at Week 24.ResultsBetween March 6, 2019 and February 1, 2021, 22 patients received darvadstrocel and completed the 52-week follow-up. The proportion of patients achieving combined remission at Week 24 was 59.1% (95% confidence interval [CI], 38.5–79.6). The effect was maintained at Week 52, with 68.2% [95% CI, 48.7–87.6] of patients achieving combined remission. Treatment-related adverse events included: one [4.5%] patient with worsening of Crohn’s disease and diarrhoea, and one [4.5%] patient with blood bilirubin increase. No new safety findings were identified in this study.ConclusionsThe efficacy and tolerability of darvadstrocel in Japanese adult patients with treatment-refractory complex perianal fistulas in Crohn’s disease were similar to those observed in the previous European study. ClinicalTrials.gov number, NCT03706456.
Cardiogenic shock due to Takotsubo cardiomyopathy associated with thyroid crisis: a case report
Authors: Fan Xiaojuan , Liu Ping , Bai Ling 
Published: September 2022

Abstract

Background
The development of cardiogenic shock due to the coexistence of Takotsubo cardiomyopathy and thyroid crisis in patients has been scarcely reported.

Case summary
A 46-year-old female presented with chest pain, palpitations, nausea, and vomiting for 8 h. She was initially considered to have acute myocardial infarction due to elevated cardiac markers and abnormal electrocardiogram changes. Immediately after the coronary angiography revealed a normal coronary artery, the patient developed refractory cardiogenic shock. Echocardiography demonstrated a typical apical ballooning type of Takotsubo cardiomyopathy with a left ventricular ejection fraction (LVEF) of 32%. A combination of norepinephrine and dopamine and an intra-aortic balloon pump (IABP) was used to support haemodynamic stability but failed to improve the patient’s condition. Immediately after the laboratory tests revealed previously unknown hyperthyroidism on the second hospital day, a rapid atrial fibrillation (AF) suddenly occurred. Nifekalant successfully restored sinus rhythm in a short time. The patient persistently complained of chest tightness, palpitations, and sweating for the first 4 days until levosimendan and antithyroid crisis treatment were used.

Discussion
Takotsubo cardiomyopathy and thyroid crisis can co-occur and present as cardiogenic shock. In the presence of severe cardiac dysfunction and untreated hyperthyroidism, nifekalant is an ideal option for the new onset of AF. The combination of heart failure treatment and antithyroid crisis drugs can effectively restore cardiac function and is associated with good clinical outcomes.
Case report of a peripheral artery disease patient with its aetiology clarified by retrograde angioscopy
Authors: Yamane Haruya , Ueda Yasunori , Ikeoka Kuniyasu , Kosugi Shumpei 
Published: September 2022

Abstract

Background
Angioscopy plays an important role providing much information regarding vessel surfaces as macro-pathology in living patients. However, its viewing field is sometimes limited due to insufficient removal of blood flow and a catheter that cannot be controlled to view the intended direction. Angioscopy from a retrograde approach was found to overcome these limitations.

Case summary
A 68-year-old man was admitted to our hospital with acute intermittent claudication for 2 weeks. He was diagnosed with acute limb ischaemia (ALI) in his left superficial femoral artery, and revascularization by endovascular treatment was attempted. A bi-directional approach was needed for successful revascularization with thrombus aspiration and angioplasty. Subsequent angioscopic examination from the retrograde approach visualized a clear and adequate image of the vessel and helped identify the aetiology of the case as on-site thrombosis at an atherosclerotic lesion.

Discussion
It is important to understand the aetiology of ALI in each case for the management of the patient. Angioscopy can be a useful modality to identify the aetiology. It was found that retrograde angioscopy has several advantages over antegrade angioscopy in clear visualization and intentional control of the angioscopy catheter. This methodology may help us identify the aetiology of ALI by evaluating the vessel walls of patients with peripheral artery disease more precisely.
Abiotrophia defectiva endocarditis of bicuspid aortic valve: a case report
Authors: Fakhra Sadaf , Javaid Awad , Shafi Amaan , Ahsan Chowdhury 
Published: September 2022

Abstract

Background
Patients with a bicuspid aortic valve have increased risk of infective endocarditis, but common organisms are not always the culprit. We describe a case of an otherwise healthy young gentleman with bicuspid aortic valve who experienced Abiotrophia defectiva endocarditis. The aim of this case report is to highlight an uncommon cause of endocarditis associated with significant morbidity and mortality in order to improve the care provided by trainees and clinicians.

Case summary
A 37-year-old male presented with a 1-month history of fever, weight loss, myalgia, and night sweats. On transoesophageal echocardiography, he was found to have a bicuspid aortic valve with large vegetation and severe aortic insufficiency. Blood cultures were positive for A. defectiva. The endocarditis was successfully treated with surgical aortic valve replacement and 6 weeks of antibiotic therapy.

Discussion
Bicuspid valves are known to have increased susceptibility to endocarditis. The difficulty of isolating A. defectiva typically leads to delayed diagnosis and significant complications. This case is a reminder to have a high degree of suspicion for organisms which are rare and difficult to isolate because prompt recognition and surgical intervention may improve the outcome of care.
Successful treatment of doxorubicin-induced cardiomyopathy with low-dose sacubitril/valsartan: a case report
Authors: Bell Elisabeth , Desuki Alexander , Karbach Susanne , Göbel Sebastian 
Published: September 2022

Abstract

Background
Cancer therapy–related cardiac dysfunction (CTRCD) is a challenging and life-threatening complication of many chemotherapeutic regimens. CTRCD prevention, diagnosis, and therapy require both careful interdisciplinary assessment and management. For patients with CTRCD, current guidelines of the European Society of Cardiology (ESC) recommend an angiotensin-converting-enzyme inhibitor in combination with a beta-blocker. Recent studies indicate a beneficial effect of sacubitril/valsartan in this patient population.

Case summary
A 68-year-old female patient with a pleural epithelioid angiosarcoma developed heart failure with reduced ejection fraction and elevated serum biomarkers following doxorubicin treatment. After implementation of a recommended cardioprotective medical therapy including torasemide, ramipril, carvedilol, and spironolactone, the patient suffered two cardiac decompensations within 4 weeks after initiation of a paclitaxel regimen and pleural radiation therapy due to pain exacerbation. Despite a continuous application of the cardioprotective medical treatment regimen, no improvement of left-ventricular ejection fraction (LVEF) was detected in a 4-month follow up. Interestingly, after omitting ramipril and implementing low-dose sacubitril/valsartan (26/24 mg), we observed a decrease in serum biomarkers within 3 months as well as a significant improvement of LVEF within 6 months. After nearly 10 months of disease stabilization under paclitaxel, the patient suffered progressive cancer disease and deceased 1 week later after the initiation of a therapeutic attempt with pazopanib.

Discussion
This case report highlights the importance of interdisciplinary care in cancer patients as well as the promising role of (low-dose) sacubitril/valsartan in patients with CTRCD even in the setting of delayed initiation.
Arrhythmogenic right-ventricular cardiomyopathy with plakophilin-2 genetic variant concomitant with early manifestation of ventricular tachyarrhythmia: a case series
Authors: Kawano Kyoko , Kondo Hidekazu , Takahashi Masaki , Shinohara Tetsuji , Ohno Seiko , Horie Minoru , Takahashi Naohiko 
Published: September 2022

Abstract

Background
Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy characterized by fibro-fat replacement of the right-ventricular myocardium. There are many factors associated with poor prognosis in patients with ARVC. Among these factors, intensive physical exertion is considered an important risk factor for sudden cardiac death.

Case summary
Herein, we report a case series of siblings with ARVC and an early manifestation of ventricular tachyarrhythmia. Plakophilin-2 (PKP2) genetic variant, which is one of the causative genetic variants of ARVC, was detected by genetic testing in all three siblings. They were young athletes with lethal/symptomatic ventricular tachycardias. The eldest sibling was implanted with a transvenous implantable cardioverter defibrillator (ICD) due to resuscitated cardiopulmonary arrest at 18 years of age; the next oldest patient was treated with successful catheter ablation at 17 years; the youngest patient was treated with catheter ablation and subcutaneous ICD implantation at 17 years.

Discussion
A recent experimental model revealed that physical exertion in PKP2 knockout mice diminished cardiac muscle mass and increased cardiac myocyte apoptosis, despite enhanced arrhythmogenicity such as increased fractional shortening and calcium transient amplitude. The three siblings were heterozygous for the previously reported pathologic splice site variant c.2489 + 1G &gt; A in Intron 12 of the PKP2. The variant might play an important role in facilitating the vulnerability to arrhythmia under intensive endurance training. Most ARVC patients with PKP2 variant, especially pathologic splice site variant c.2489 + 1G &gt; A in Intron 12 of the PKP2, might have to be managed strictly regarding daily exercise.
Su(var)2-10- and Su(var)205-dependent upregulation of the heterochromatic gene neverland is required for developmental transition in Drosophila
Authors: Ohhara Yuya , Kato Yuki , Kamiyama Takumi , Yamakawa-Kobayashi Kimiko 
Published: September 2022

Abstract
Animals develop from juveniles to sexually mature adults through the action of steroid hormones. In insect metamorphosis, a surge of the steroid hormone ecdysone prompts the transition from the larval to the adult stage. Ecdysone is synthesized by a series of biosynthetic enzymes that are specifically expressed in an endocrine organ, the prothoracic gland. At the late larval stage, the expression levels of ecdysone biosynthetic enzymes are upregulated through the action of numerous transcription factors, thus initiating metamorphosis. In contrast, the mechanism by which chromatin regulators support the expression of ecdysone biosynthetic genes is largely unknown. Here, we demonstrate that Su(var)2-10 and Su(var)205, suppressor of variegation [Su(var)] genes encoding a chromatin regulator Su(var)2-10 and nonhistone heterochromatic protein 1a, respectively, regulate the transcription of one of the heterochromatic ecdysone biosynthetic genes, neverland, in Drosophila melanogaster. Knockdown of Su(var)2-10 and Su(var)205 in the prothoracic gland caused a decrease in neverland expression, resulting in a defect in larval-to-prepupal transition. Furthermore, overexpression of neverland and administration of 7-dehydrocholesterol, a biosynthetic precursor of ecdysone produced by Neverland, rescued developmental defects in Su(var)2-10 and Su(var)205 knockdown animals. These results indicate that Su(var)2-10- and Su(var)205-mediated proper expression of neverland is required for the initiation of metamorphosis. Given that Su(var)2-10-positive puncta are juxtaposed with the pericentromeric heterochromatic region, we propose that Su(var)2-10- and Su(var)205-dependent regulation of inherent heterochromatin structure at the neverland gene locus is essential for its transcriptional activation.
Intrinsic base substitution patterns in diverse species reveal links to cancer and metabolism
Authors: Gelova Suzana P , Doherty Kassidy N , Alasmar Salma , Chan Kin 
Published: September 2022

Abstract
Analyses of large-scale cancer sequencing data have revealed that mutagenic processes can create distinctive patterns of base substitutions, called mutational signatures. Interestingly, mutational patterns resembling some of these signatures can also be observed in normal cells. To determine whether similar patterns exist more generally, we analyzed large data sets of genetic variation, including mutations from 7 model species and single nucleotide polymorphisms in 42 species, totaling &gt;1.9 billion variants. We found that base substitution patterns for most species closely match single base substitution (SBS) mutational signature 5 in the Catalog of Somatic Mutations in Cancer (COSMIC) database. SBS5 is ubiquitous in cancers and also present in normal human cells, suggesting that similar patterns of genetic variation across so many species are likely due to conserved biochemistry. We investigated the mechanistic origins of the SBS5-like mutational pattern in Saccharomyces cerevisiae, and show that translesion DNA synthesis and sugar metabolism are directly linked to this form of mutagenesis. We propose that conserved metabolic processes in cells are coupled to continuous generation of genetic variants, which can be acted upon by selection to drive the evolution of biological entities.
The Role of Incarceration as a Risk Factor for Cognitive Impairment
Authors: Cox Robynn J A , Wallace Robert B 
Published: September 2022

Abstract

Objectives
The objective of this study was to understand disparities in cognitive impairment between middle-aged formerly incarcerated (FI) and nonincarcerated individuals.

Methods
The 1979 National Longitudinal Survey of Youth is a nationally representative longitudinal data set containing information on incarceration, cognitive functioning, and other health conditions. Using a modified version of the Telephone Interview for Cognitive Status (TICS-m), adapted from the Health and Retirement Study, we analyzed the association between incarceration and cognitive impairment, cognitive impairment—not dementia and dementia. Multivariable regression models were estimated, including prior incarceration status and covariates associated with incarceration and cognitive functioning.

Results
FI individuals had lower unadjusted scores on TICS-m (−2.5, p &lt; .001) and had significantly greater unadjusted odds ratios (OR) for scoring in the cognitive impairment (OR = 2.4, p &lt; .001) and dementia (OR = 2.7, p &lt; .001) range. Differences were largely explained by a combination of risk factors associated with incarceration and cognition. Education and premorbid cognition (measured by Armed Forces Qualification Test) separately and completely explained differences in the odds of dementia. Regardless of incarceration status, Blacks and Hispanics had significantly greater odds of cognitive impairment and dementia relative to Whites, holding other factors constant.

Discussion
The association between prior incarceration and cognitive impairment in middle age was largely explained by differences in educational attainment and premorbid cognitive functioning, supporting the cognitive reserve hypothesis. Greater prevalence of cognitive impairment and dementia among the FI could create challenges and should be considered in reentry planning. Structural and institutional factors should be considered when addressing health disparities in Alzheimer’s Disease and Related Dementias.
People do care about the deep sea. A comment on Jamieson et al. (2020)
Authors: Armstrong Claire W , Aanesen Margrethe , Hynes Stephen , Tinch Rob 
Published: September 2022

Abstract
In a paper in this journal entitled “Fear and loathing of the deep sea: why don't people care about the deep sea?”, Jamieson et al. (2020) pose this question and answer it with many interesting perspectives from psychology, ocean literacy and philosophy. However, there is an inherent assumption in the question they ask that people do not care about the deep sea. In order to assess this assumption, we contend that the first question to ask is: do people care about the deep sea? Based on the cultural significance of the theme of the deep ocean in art and literature, the results of ocean attitudinal surveys and the work done on deep sea economic valuation in recent years, we suggest that the answer is that people do care about many different aspects of the deep sea, not only the ones that hold market value, but also non-market values. It is nonetheless argued that the welfare benefits that societies gain from the deep sea are not at the fore in political discussions or marine policy making.
Reply to: People do care about the deep sea. A comment on Jamieson et al. (2020)
Authors: Jamieson Alan J , Linley Thomas D , Arasu Prema 
Published: September 2022

Abstract
Why don’t people care about the deep sea? was a question addressed in a 2020 Food for Thought article in this journal. That article delivered an extensive critique of misleading statements, poorly structured analogies, and common misconceptions to challenge the largely negative or unnecessarily sensationalist narrative when the deep sea is communicated to the public. The overarching sentiment of that article has been countered by a Comment in which it is argued that people do in fact care about the deep sea. However, this counter argument is based on very little to do with the deep sea but rather a corpus of studies relating mostly to cold water corals and people’s willingness to pay for their conservation and restoration in the event of impending or recent destruction. We do not feel that the Comment addresses the same problem as discussed in the original article. Here, we explain that the seeming differences of opinion about whether people care about the deep sea are based on two things: the title of the article commented on (not its content) and how the original article, and the Comment on it, define the deep sea.
Prevalence of inverse psoriasis subtype with immune checkpoint inhibitors
Authors: Jfri Abdulhadi , Leung Bonnie , Said Jordan T , Semenov Yevgeniy , LeBoeuf Nicole R 
Published: September 2022

Summary

Background
Cutaneous immune-related adverse events (irAEs) are the most common irAEs caused by immune-checkpoint inhibitors (ICI). Psoriasiform eruptions, both de novo and flares, may occur. Evidence is lacking on inverse psoriasis subtype.

Methods
A retrospective study was conducted at Dana-Farber Cancer Institute/Mass General Brigham through February 2020 using databases. Confirmed inverse psoriasis cases pre-/post-ICI initiation either independently or in conjunction with other psoriasis subtypes were included. Known psoriasis cases without flare post-ICI were excluded.

Results
A total of 262 (3%) individuals with any ICI-mediated psoriasiform cutaneous irAE were identified out of the 8683 DFCI ICI-treated patients. Of these, 13 (5% of psoriasis patients) had inverse psoriasis (mean age 68.7 years; 7/13 male sex). Median (range) time from ICI initiation to inverse psoriasis development or flare was 7 (4–12) and 3.5 (2–6) weeks, respectively. Pruritus occurred in 12/13 (92.30%) cases. 11 (85%) had inguinal involvement; other sites included gluteal cleft (6; 46%), inframammary (3; 23%), perianal (2; 15%), axilla (2; 15%), umbilicus (2; 15%), and infra-abdominal folds (1; 8%). Most (9/13) individuals had more than one site involved. The Common Terminology Criteria for Adverse Events severity was 1 in 10 (76.92%) individuals and 2 in 3 (15.38%) individuals. Six (46.15%) patients were treated initially by oncology with topical (nystatin, econazole, or clotrimazole) or systemic antifungals (fluconazole) for median (range) of 3.5 (1–7) months without improvement, for presumed candida intertrigo.

Conclusion
Patients on ICI may develop inverse psoriasis, which may be initially confused for fungal intertrigo. Delayed diagnosis can prolong symptoms, while patients are treated ineffectively with topical/systemic antifungals for presumed candida infection. Oncologist and dermatologist awareness is important to improve diagnosis of ICI-mediated inverse psoriasis, its management and affected patients’ quality of life.
On the BBM-Phenomenon in Fractional Poincaré–Sobolev Inequalities with Weights
Authors: Hurri-Syrjänen Ritva , Martínez-Perales Javier C , Pérez Carlos , Vähäkangas Antti V 
Published: September 2022

Abstract
In this paper, we unify and improve some of the results of Bourgain, Brezis, and Mironescu and the weighted Poincaré–Sobolev estimate by Fabes, Kenig, and Serapioni. More precisely, we get weighted counterparts of the Poincaré–Sobolev-type inequality and also of the Hardy type inequality in the fractional case under some mild natural restrictions. A main feature of the results we obtain is the fact that we keep track of the behavior of the constants involved when the fractional parameter approaches to $1$. Our main method is based on techniques coming from harmonic analysis related to the self-improving property of generalized Poincaré inequalities.