bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia
Authors: Coats Thomas , Bean Daniel , Basset Aymeric , Sirkis Tamir , Brammeld Jonathan , Johnson Sean , Thomas Ian , Gilkes Amanda , Raj Kavita , Dennis Mike , Knapper Steve , Mehta Priyanka , Khwaja Asim , Hunter Hannah , Tauro Sudhir , Bowen David , Jones Gail , Dobson Richard , Russell Nigel , Dillon Richard
Published: December 2021

Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front‐line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real‐world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available.
Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant
Authors: Braz S. V. , Benicio R. A. , Tonelli G. S. S. S. , Báo S. N. , Moretti P. N. , Pic-Taylor A. , Oliveira S. F. , Acevedo A. C. , Costa I. M. C. , Mazzeu J. F.
Published: December 2021

Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin-related disorders. We report a patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation.

Click https://www.wileyhealthlearning.com/#/online-courses/a6ef1275-8325-4834-89d2-aa18fa31e63f for the corresponding questions to this CME article.
Glycomics reveal that ST6GAL1‐mediated sialylation regulates uterine lumen closure during implantation
Authors: Han Kun , Wang Feiyu , Yue Yulu , Tan Xihong , Tian Miao , Miao Yiliang , Zhao Shuhong , Dong Weijie , Yu Mei
Published: December 2021

Objectives

Implantation failure is a major cause of prenatal mortality. The uterine lumen closure contributes to embryo adhesion to the uterus, but its underlying mechanisms are largely unknown. Our previous study has reported that endometrial fold extension can lead to uterine lumen closure in pigs. The objective of this study was to reveal molecular mechanisms of the uterine lumen closure by characterizing the molecular basis of the endometrial fold extension during implantation in pigs.

Materials and methods

Uterine and endometrium tissues during implantation were collected in pigs. MALDI‐TOF MS was used to characterize the N‐glycomic profiles. Histochemistry, siRNA transfection, Western blotting, lectin immumoprecipitation, mass spectrometry and assays of wounding healing and cell aggregation were performed to investigate the molecular basis.

Results

We observed that uterine luminal epithelium (LE) migrated collectively during endometrial fold extension. For the first time, we identified a large number of N‐glycan compositions from endometrium during implantation using MALDI‐TOF MS. Notably, the α2,6‐linked sialic acid and ST6GAL1 were highly expressed in uterine LE when the endometrial folds extended greatly. Subsequently, the role of ST6GAL1‐mediated 2,6‐sialylation in collective epithelial migration was demonstrated. Finally, we found that ST6GAL1‐mediated α2,6‐sialylation of E‐cadherin may participate in collective migration of uterine LE.

Conclusions

The study reveals a mechanism of uterine lumen closure by identifying that ST6GAL1‐mediated α2,6‐sialylation of cell adhesion molecules contributes to endometrial fold extension through regulating collective migration of uterine LE.
Human hope and the reign of God
Authors: Jeanrond Werner G.
Published: December 2021

This article discusses the theological virtue of hope in relation to the Christian expectation of God's coming reign. Hope, as distinct from optimism and from all sorts of individualistic hopes, refers to God's gift of future. Hence, the tension between expecting God's coming reign, on the one hand, and the challenge of living constructively in the here and now, on the other hand, engages theological approaches to hope. It is argued that the divine gift of love, rather than faith, provides the main source of orientation for the Jewish and the Christian praxis of hope in this world. Faith is often understood in terms of assent to certain doctrinal definitions, while the other dimension of faith, God's offer of relationship, has moved to the background. Accepting love as guide to the Christian praxis of hope strengthens the relational nature of hope. No one can hope for herself or himself alone. The Gospels and the Pauline letters confirm the centrality of love for Christian discipleship. The article concludes with, first, a discussion of the contemporary challenge of migration; and, second, with a consideration of the connection between hope for personal fulfilment and hope for the future of the universe. Both examples point to a theology that is inspired by love and equipped to approach Christian discipleship in a spirit of hope.
Estimating the cost of type 1 diabetes in Ireland
Authors: Sharma Shikha , Gillespie Paddy , Hobbins Anna , Dinneen Sean F.
Published: December 2021

Background

Type 1 diabetes is a chronic disease, which given its existing and projected prevalence, is likely to pose a significant economic burden, both in terms of directs costs to the healthcare system and indirect costs to society. We aimed to estimate the economic burden of type 1 diabetes in Ireland, which at present, is unknown.

Methods

A cost of illness study was undertaken to estimate the cost of type 1 diabetes in Ireland for 2018. Data for prevalence, morbidity, mortality, healthcare resource use, absenteeism, and unit costs were obtained from national, and where necessary, international sources. Direct healthcare costs were estimated for primary care, outpatient, emergency and inpatient care, for associated complications, structured education programmes, insulin and related care. Additionally, indirect costs from lost earnings due to premature death and employee absenteeism were estimated.

Results

Type 1 diabetes was estimated to cost €129 million in Ireland in 2018, with direct healthcare costs accounting for €81.5 million or 63% and indirect costs for €47.5 million or 37% of the total. On average, this amounted to €3994 per patient in direct healthcare costs and €2326 per patient in indirect costs.

Conclusion

Type 1 diabetes is a leading public health problem. Our study is the first to assess the economic burden of type 1 diabetes in Ireland, and our results should be informative to policymakers tasked with prioritising healthcare and research funding resource allocation.
MAKING THE CASE AGAINST PARAGRAPH 218: NARRATIVE AND DISCURSIVE STRATEGIES IN ELSE KIENLE'S FRAUEN: AUS DEM TAGEBUCH EINER ÄRZTIN★
Authors: Calvert Katherine E.
Published: December 2021

This article analyses Dr Else Kienle's 1932 text Frauen: Aus dem Tagebuch einer Ärztin within the context of the debates around women's access to abortion in Weimar Germany. Access to abortion was a widely debated topic in Weimar Germany and public demonstrations against Paragraph 218 of the Weimar penal code, which outlawed abortion, occurred following the 1931 arrest of Dr Kienle. I argue that, as a non‐partisan work written from the perspective of a practising doctor, Kienle's text offers an innovative contribution to these debates. While Kienle's arrest is frequently cited as a key moment in the Weimar abortion debates, her writing has received limited critical attention. My analysis of the literary and discursive strategies employed by Kienle in Frauen: Aus dem Tagebuch einer Ärztin reveals that Kienle goes beyond the arguments of the women's and socialist movements. Kienle's text should be read as an attempt to broaden the reach of the campaign against Paragraph 218. The book adopts an innovative and experience‐led approach, which reveals the medical, psychological, and social implications of limiting women's access to abortion, and which only re‐emerged in the Federal Republic of Germany in the 1970s.
Antibiotic resistance patterns and therapeutic outcomes of pediatric Helicobacter pylori infection in a high‐migrant Singaporean cohort
Authors: Huang James Guoxian , Lim Si Ying Sheryl , Aw Marion Margaret , Quak Seng‐Hock
Published: December 2021

Background

Variation in Helicobacter pylori (H. pylori) disease in terms of prevalence and antibiotic resistance prevails globally requiring a need to develop region‐specific surveillance. We aimed to assess the influence of immigration factors upon the interpretation of local Singaporean epidemiological trends in antimicrobial susceptibility patterns and therapeutic outcomes in children with culture‐positive H. pylori.

Materials and Methods

We retrospectively analyzed eradication outcomes of children with culture‐proven H. pylori infections between 2011 and 2020 at our center, and we also analyzed the antimicrobial susceptibility profiles of the corresponding H. pylori isolates. The cohort was classified into two groups: (1) Native Singaporeans and (2) Non‐native Singaporeans (First‐/Second‐generation immigrants and Non‐residents) to correlate with resistance patterns and eradication outcomes. H. pylori culture was done via Kirby‐Bauer disk diffusion for the era 2011–2016 and bioMérieux E test for 2016–2020.

Results

A total of 70 children (median age 14 [2–17] years) were included in the analysis. 42.9% (30/70) of the cohort displayed some form of antibiotic resistance; clarithromycin resistance was the most prevalent (30.0%), followed by metronidazole (27.5%) and amoxicillin (7.1%). Comparing to natives, non‐native Singaporeans were significantly younger at presentation (mean 11.7 vs. 13.7 years, p = 0.043), and a significantly higher proportion of non‐natives carried clarithromycin‐resistant (51.4% vs. 8.6%, p < 0.001), metronidazole‐resistant (47.1% vs. 8.6%, p < 0.001), or multidrug‐resistant (resistant to ≥2 drugs) (40.0% vs. 2.9%, p < 0.001] strains. Non‐natives were significantly more likely to fail first‐line eradication therapy (48.5% failure vs. 23.3%, p = 0.038). The proportion of pan‐sensitive H. pylori was significantly lower in first‐generation (25.0%, p = 0.001) and second‐generation (42.9%, p = 0.018) immigrants compared to natives (82.86%). These conclusions did not vary when the analysis was repeated for each culture method.

Conclusions

An antibiotic susceptibility‐based approach should be advocated for all patients but especially so for non‐natives, who are at higher risk for antimicrobial resistant strains and poorer eradication outcomes.
Unravelling undifferentiated soft tissue sarcomas: insights from genomics
Authors: Hames-Fathi Shadi , Nottley Steven W G , Pillay Nischalan
Published: December 2021

Undifferentiated pleomorphic sarcoma now falls under the broader rubric of undifferentiated soft tissue sarcoma (USTS) in the 2020 World Health Organization classification of bone and soft tissue tumours. These rare cancers remain a diagnosis of exclusion, and show genomic complexity manifesting as extreme forms of aneuploidy and genetic rearrangement. This review covers some of the recent advances in the diagnosis and treatment of USTS based on genomic sequencing, cancer evolution and heterogeneity studies, and immunotherapy. We highlight the critical role that pathologists have to play in the diagnosis and treatment of patients with USTS, viewed through the lens of the hallmarks of cancer.
Evolving classification of rhabdomyosarcoma
Authors: Agaram Narasimhan P
Published: December 2021

Rhabdomyosarcomas comprise the single largest category of soft tissue sarcomas in children and adolescents in the United States, occurring in 4.5 million people aged below 20 years. Based on the clinicopathological features and genetic abnormalities identified, rhabdomyosarcomas are classified into embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. Each subtype shows distinctive morphology and has characteristic genetic abnormalities. This review discusses the evolution of the classification of rhabdomyosarcoma to the present day, together with a discussion of key histomorphological and genetic features of each subtype and the diagnostic approach to these tumours.
Recent advances in the diagnosis, classification and molecular pathogenesis of cutaneous mesenchymal neoplasms
Authors: Papke D J , Hornick J L
Published: December 2021

The diagnosis of cutaneous mesenchymal neoplasms remains challenging, due to a combination of overlapping histological features, the rarity of some diagnoses and often inadequate sampling in superficial biopsies. Here, we describe recent advances in cutaneous mesenchymal neoplasms. We discuss improvements in our understanding of the molecular pathogenesis of non‐neural granular cell tumour, epithelioid fibrous histiocytoma, composite and retiform haemangioendothelioma and dermatofibrosarcoma protuberans. We also discuss recently described tumour types, including some discovered via molecular testing:EWSR1::SMAD3‐rearranged fibroblastic tumour, clear cell neoplasm withMITF::CREMrearrangement and melanocytoma withCRCT1::TRIM11rearrangement, and some discovered via traditional histopathology: superficial CD34‐positive fibroblastic tumour, plexiform myofibroblastoma and clear cell neoplasm with melanocytic differentiation andACTIN::MITFtranslocation.
The genetics of vascular tumours: an update
Authors: Torrence Dianne , Antonescu Cristina R
Published: December 2021

Recent molecular advances have shed significant light on the classification of vascular tumours. Except for haemangiomas, vascular lesions remain difficult to diagnose, owing to their rarity and overlapping clinical, radiographic and histological features across malignancies. In particular, challenges still remain in the differential diagnosis of epithelioid vascular tumours, including epithelioid haemangioma and epithelioid haemangioendothelioma at the benign/low‐grade end of the spectrum, and epithelioid angiosarcoma at the high‐grade end. Historically, the classification of vascular tumours has been heavily dependent on the clinical setting and histological features, as traditional immunohistochemical markers across the group have often been non‐discriminatory. The increased application of next‐generation sequencing in clinical practice, in particular targeted RNA sequencing (such as Archer, Illumina), has led to numerous novel discoveries, mainly recurrent gene fusions (e.g. those involving FOS, FOSB, YAP1, and WWTR1), which have resulted in refined tumour classification and improved diagnostic reproducibility for vascular tumours. However, other molecular alterations besides fusions have been discovered in vascular tumours, including somatic mutations (e.g. involving GNA family and IDH genes) in a variety of haemangiomas, as well as copy number alterations in high‐grade angiosarcomas (e.g. MYC amplifications). Moreover, the translation of these novel molecular abnormalities into diagnostic ancillary markers, either fluorescence in‐situ hybridisation probes or surrogate immunohistochemical markers (FOSB, CAMTA1, YAP1, and MYC), has been remarkable. This review will focus on the latest molecular discoveries covering both benign and malignant vascular tumours, and will provide practical diagnostic algorithms, highlighting frequently encountered pitfalls and challenges in the diagnosis of vascular lesions.
Advances in the classification of round cell sarcomas
Authors: Le Loarer Francois , Baud Jessica , Azmani Rihab , Michot Audrey , Karanian Marie , Pissaloux Daniel
Published: December 2021

Round cell sarcomas represent a diagnostic challenge for pathologists, owing to the poorly differentiated features of these high‐grade tumours. The diagnosis of round cell sarcoma requires large immunohistochemical panels and molecular testing in many cases. This spectrum of malignancies is largely dominated by Ewing sarcomas (ESs), which represent the most common family of these tumours. Nonetheless, new families have been delineated in the past few years, with the addition of two additional families in the 2020 World Health Organization classification of bone and soft tissue tumours, namely sarcomas with CIC rearrangements and sarcomas with BCOR alterations. EWSR1, one of the genes involved in the driver fusion of ESs, is also implicated in the translocation of many other tumours with heterogeneous lineages and variable levels of aggressiveness. Round cell sarcomas associated with fusions inwhichEWSR1is partnered with genes encoding transcription factors distinct from those of the ‘Ewing family’ represent a heterogeneous group of rare tumours that require further study to determine whether their fusions may or not define a specific subgroup. They include mainly sarcomas with NFATc2 rearrangements and sarcomas with PATZ1 rearrangements. At this point, PATZ1 fusions seem to be associated with tumours of high clinical and morphological heterogeneity. Molecular studies have also helped in the identification of more consistent biomarkers that give tremendous help to pathologists in triaging, if not diagnosing, these tumours in practice. This review compiles the latest accumulated evidence regarding round cell sarcomas, and discusses the areas that are still under investigation.
Superior even skin tone and anti‐ageing benefit of a combination of 4‐hexylresorcinol and niacinamide
Authors: Shariff Rezwan , Du Yaping , Dutta Maitreyee , Kumar Satish , Thimmaiah Sreenivasa , Doraiswamy Chandraprabha , Kumari Annu , Kale Vaidehi , Nair Nirmala , Zhang Shuliang , Joshi Manoj , Santhanam Uma , Qiang Qiu , Damodaran Anita
Published: December 2021

Objectives

To demonstrate the synergistic effect of 4‐hexylresorcinol (4‐HR) with niacinamide in boosting anti‐melanogenic efficacy in vitro and establish the in vivo efficacy and safety of the combination in a human trial.

Methods

Primary human epidermal melanocytes and 3D pigmented skin equivalents were treated with 4‐HR, niacinamide, and their combinations for their effect on pigmentation. This was followed by a randomized, double‐blind, split‐face clinical study in Chinese subjects, and effects on skin tone, hyperpigmentation, fine lines and wrinkles, hydration, and skin firmness were measured for a 12‐week study period.

Results

In vitro tyrosinase enzyme activity studies showed that 4‐HR is one of the most potent tyrosinase inhibitors. The combination of 4‐HR and niacinamide showed a synergistic reduction in melanin production in cultured melanocytes and lightened the 3D skin equivalent model. In vitro as well as in the human trial, the combination of 4‐HR and niacinamide showed significantly improved efficacy over niacinamide alone on hyperpigmentation spots as measured by L*, the visual appearance of fine lines and wrinkles in crow's feet and perioral area and skin firmness, with no product‐related adverse events.

Conclusions

A formulation containing a combination of 4‐HR and niacinamide delivered superior skin tone and anti‐ageing benefits significantly better than niacinamide alone with no adverse events. This study demonstrates that a product designed to affect multiple pathways of melanogenesis, inflammation, and ageing may provide an additional treatment option, beyond hydroquinone and retinoids, for hyperpigmentation and ageing.
HbA1c level may be a risk factor for oxygen therapy requirement in patients with coronavirus disease 2019
Authors: Yanagisawa Shinnosuke , Oikawa Yoichi , Takagi Sotaro , Horikoshi Yuta , Satomura Atsushi , Imai Kazuo , Sakai Jun , Ishibashi Noriomi , Tarumoto Norihito , Iida Shinichiro , Nakayama Hideto , Haga Yoshiyuki , Maesaki Shigefumi , Shimada Akira
Published: December 2021

Introduction

Many clinical studies have identified significant predictors or risk factors for the severity or mortality of coronavirus disease 2019 (COVID‐19) cases. However, there are very limited reports on the risk factors for requiring oxygen therapy during hospitalization. In particular, we sought to investigate whether plasma glucose and HbA1c levels could be risk factors for oxygen therapy requirement.

Materials and Methods

A single‐center, retrospective study was conducted of 131 COVID‐19 patients hospitalized at Saitama Medical University Hospital between March 2020 and November 2020. To identify the risk factors for oxygen therapy requirement during hospitalization, a stepwise multivariate binary logistic regression analysis was performed using several clinical parameters commonly obtained on admission, including plasma glucose and HbA1c levels.

Results

Of the 131 patients with COVID‐19, 33.6% (44/131) received oxygen therapy during hospitalization. According to the logistic regression analysis, male sex (odds ratio [OR]: 8.76, 95% confidence interval [CI]: 1.65–46.5, P < 0.05), age (OR: 1.07, 95% CI: 1.02–1.12, P < 0.01), HbA1c levels (OR: 1.94, 95% CI: 1.09–3.44, P < 0.05), and serum C‐reactive protein (CRP) levels (OR: 2.22, 95% CI: 1.54–3.20, P < 0.01) emerged as independent variables associated with oxygen therapy requirement during hospitalization.

Conclusions

In addition to male sex, age, and serum CRP levels, HbA1c levels on admission may serve as a risk factor for oxygen therapy requirement during the clinical course of COVID‐19, irrespective of diabetes history and status. This may contribute to the efficient delegation of limited numbers of hospital beds to patients at risk for oxygen therapy requirement.
Atlantic mackerel (Scomber scombrus) change skin colour in response to crowding stress
Authors: Tveit Guro M. , Anders Neil , Bondø Morten S. , Mathiassen John R. , Breen Mike
Published: December 2021

Wild capture can be stressful for fish. Stress has the potential to induce mortality in released unwanted catches or negative flesh quality consequences in retained ones. Such effects compromise sustainable natural resource management and industry profitability. Mitigating stress during capture is therefore desirable. Biological indicators of stress can objectively inform fishers as to the functional welfare status of catches during fishing operations. If they are to be of practical use in mitigating stress during wild capture events, such indicators must be quantifiable, respond rapidly, reflect the level of induced stress and be easily observable. Atlantic mackerel (Scomber scombrus) are extensively targeted by purse seine fisheries in European waters but are particularly vulnerable to stress. Excessive crowding in the net is thought to be the principal stress mechanism. There is therefore a need to develop indicators of crowding stress for this species so that catch welfare can be improved. Here, we demonstrate that S. scombrus exhibit a skin colour change from predominately green to predominately blue when exposed to crowding stress. In sea cage trials, we induced various degrees of stress in groups of wild‐caught S. scombrus by manipulating crowding density and its duration. Skin colour was quantified in air using digital photography. The colour change occurred rapidly (within the typical duration of crowding events in the fishery), and its magnitude was correlated to the severity and duration of crowding. Bluer fish were also associated with higher levels of plasma lactate. No appreciable colour change was observed in uncrowded (control) groups during the treatment period. Nonetheless, unstressed S. scombrus did turn blue <1 h after death. Together, these results indicate that skin colour change has the potential to be a useful real‐time indicator of crowding stress for S. scombrus and could therefore be used to improve welfare during wild capture fishing.
Transposing flood risk from extreme rainfall events: A case study of Hurricane Harvey
Authors: Regier Elizabeth , Naughton Joseph , McDonald Walter
Published: December 2021

Hurricane Harvey produced unprecedented flooding that altered flood frequency statistics near Houston, Texas. While Harvey could have made landfall elsewhere along the Gulf coast, traditional flood frequency methodologies only consider the risk of Harvey in the region that it hit. This may be a shortcoming of flood frequency methodologies as the intensity of Harvey was greater due to climate change; therefore, Harvey may be more indicative of future hurricanes than other historical observations. To that end, this study investigates what effect Harvey would have had on flood frequency statistics if it had made landfall elsewhere. To do so, a Monte Carlo simulation was used to shift Harvey's rainfall within alternative landfall locations. This rainfall was then applied to synthetic unit hydrographs to estimate peak flows that were applied in Log Pearson III and Regional Flood Frequency Analyses. Log Pearson III analyses with simulated Harvey streamflows produced median 100‐year peak flows that were 17%–66% higher than analyses that only used historical records. A regional flood frequency analysis in the central coastal geomorphologic region of Texas showed that predictive equations, based upon basin area and shape factor, had an average increase of 30.2% in the 100‐year peak discharge.
Spermidine supplementation influences mitochondrial number and morphology in the heart of aged mice
Authors: Messerer Jil , Wrede Christoph , Schipke Julia , Brandenberger Christina , Abdellatif Mahmoud , Eisenberg Tobias , Madeo Frank , Sedej Simon , Mühlfeld Christian
Published: December 2021

Aging is associated with cardiac hypertrophy and progressive decline in heart function. One of the hallmarks of cellular aging is the dysfunction of mitochondria. These organelles occupy around 1/4 to 1/3 of the cardiomyocyte volume. During cardiac aging, the removal of defective or dysfunctional mitochondria by mitophagy as well as the dynamic equilibrium between mitochondrial fusion and fission is distorted. Here, we hypothesized that these changes affect the number of mitochondria and alter their three‐dimensional (3D) characteristics in aged mouse hearts. The polyamine spermidine stimulates both mitophagy and mitochondrial biogenesis, and these are associated with improved cardiac function and prolonged lifespan. Therefore, we speculated that oral spermidine administration normalizes the number of mitochondria and their 3D morphology in aged myocardium. Young (4‐months old) and old (24‐months old) mice, treated or not treated with spermidine, were used in this study (n = 10 each). The number of mitochondria in the left ventricles was estimated by design‐based stereology using the Euler‐Poincaré characteristic based on a disector at the transmission electron microscopic level. The 3D morphology of mitochondria was investigated by 3D reconstruction (using manual contour drawing) from electron microscopic z‐stacks obtained by focused ion beam scanning electron microscopy. The volume of the left ventricle and cardiomyocytes were significantly increased in aged mice with or without spermidine treatment. Although the number of mitochondria was similar in young and old control mice, it was significantly increased in aged mice treated with spermidine. The interfibrillar mitochondria from old mice exhibited a lower degree of organization and a greater variation in shape and size compared to young animals. The mitochondrial alignment along the myofibrils in the spermidine‐treated mice appeared more regular than in control aged mice, however, old mitochondria from animals fed spermidine also showed a greater diversity of shape and size than young mitochondria. In conclusion, mitochondria of the aged mouse left ventricle exhibited changes in number and 3D ultrastructure that is likely the structural correlate of dysfunctional mitochondrial dynamics. Spermidine treatment reduced, at least in part, these morphological changes, indicating a beneficial effect on cardiac mitochondrial alterations associated with aging.
Prolonged use of paracetamol and the prescribing patterns on rehabilitation facilities
Authors: Jasat Homairah , Thompson John , Sonneborn Olivia , Dayment Jessica , Miller Charne
Published: December 2021

Aims and Objectives

The study investigated: (a) the usage patterns of paracetamol, and (b) the association between paracetamol use and patient outcomes such as liver and kidney functions among older people.

Background

Paracetamol is a well‐known analgesic and antipyretic drug, with an excellent safety profile when used within its recommended dose. It is a commonly used drug by people aged over 65 years to treat chronic pain. Prolonged use of paracetamol in the elderly is poorly understood. As such, there is a genuine risk among older people of unintentional overdose.

Methods

A retrospective analysis of medical records in rehabilitation wards was undertaken from 1 July 2016 to 30 June 2017. Patients' paracetamol use, prescribing patterns and biochemical results were analysed to assess for differences in admission and discharge biochemistry results. The TREND Statement was utilised to guide study reporting (Enhancing the QUAlity and Transparency Of health Research, 2021).

Results

A total of 1119 patients were admitted for seven or more days in a metropolitan tertiary hospital in Melbourne. Almost three‐quarters (74%) of patients were administered paracetamol; 76.1% received ‘Immediate‐Release Paracetamol’ (IRP), and 23.9% were given ‘Sustained‐Release Paracetamol’ (SRP). A proportion (4.5%) of patients in both the IRP and SRP groups received more than the daily recommended dose. There were limited statistically significant differences between patients' admission and discharge biochemistry results; group or time differences were observed, which were indicative of improvements within the paracetamol group.

Conclusion

Paracetamol was a commonly used medication among long‐stay elderly patients. Precaution to ensure paracetamol use does not exceed recommended daily doses is required. This study suggests that paracetamol used at a therapeutic level in older patients had limited, negative associations with liver and kidney function.

Relevance to clinical practice

The clinical practice regarding prolonged use of paracetamol is ambitious. The increased risk of paracetamol toxicity among the frail elderly is a concern. Optimising the dose adjustment in the elderly is important to avoid adverse outcomes.
Cortico‐striatal functional connectivity and cerebral small vessel disease: Contribution to mild Parkinsonian signs
Authors: Hengenius James B. , Bohnen Nicolaas I. , Rosso Andrea , Huppert Theodore J. , Rosano Caterina
Published: December 2021

Background and Purpose

Mild Parkinsonian signs (MPS) are common in older adults. We hypothesized that MPS are associated with lower functional connectivity (FC) in dopamine‐dependent cortico‐striatal networks, and these associations vary with white matter hyperintensity (WMH), a risk factor for MPS.

Methods

We examined resting‐state functional MRI in 266 participants (mean age 83; 57% female; 41% African American) with data on MPS (Unified Parkinson's Disease Rating Scale), demographics, cognition, muscle‐skeletal, and cardiometabolic health. FC between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with MPS, adjusted for covariates. Interactions of FC by WMH were tested; and analyses were repeated stratified by WMH above/below the median.

Results

Compared to those without MPS, those with MPS had lower cortico‐striatal FC in the left executive network (adjusted odds ratio [95% confidence interval], p‐value: 0.188 [0.043, 0.824], .027). The interaction with WMH was p = .064; left executive FC was inversely associated with MPS for high WMH (0.077 [0.010, 0.599], .014) but not low WMH participants (1.245 [0.128, 12.132], .850).

Conclusions

MPS appear related to lower executive network FC, robust to adjustment for other risk factors, and stronger for those with higher burden of WMH. Future longitudinal studies should examine the interplay between cerebral small vessel disease and connectivity influencing MPS.
Becoming Strong: Sociocultural Experiences, Mental Health, & Black Girls' Strong Black Woman Schema Endorsement
Authors: Anyiwo Nkemka , Stanton Alexis G. , Avery Lanice R. , Bernard Donte L. , Abrams Jasmine A. , Golden Alexandrea
Published: December 2021

This study examines the precedents and consequences of Black girls' Strong Black Woman schema (SBW) endorsement. Hierarchical regression analyses revealed that, among Black girls (N= 308), racial discrimination experiences and racial barrier socialization messages were positively associated with SBW endorsement. However, there was no significant interaction between racial discrimination and racial barrier messages in predicting SBW endorsement. Our analyses also revealed that SBW was not directly associated with internalizing symptoms (e.g., anxiety and depression symptoms). Furthermore, there was no significant interaction between racial discrimination and SBW endorsement in predicting internalizing symptoms. Findings provide evidence of and clarity on how sociocultural experiences shape SBW development and highlight a need to better understand how SBW endorsement functions in the mental health of Black girls.
Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms
Authors: Kondoh Daisuke , Nakamura Teppei , Tsuji Erika , Hosotani Marina , Ichii Osamu , Irie Takao , Mishima Takashi , Nagasaki Ken‐ichi , Kon Yasuhiro
Published: December 2021

Normal‐pressure hydrocephalus (NPH) is a condition in which the ventricle is enlarged without elevated cerebrospinal fluid pressure, and it generally develops in later life and progresses slowly. A complete animal model that mimics human idiopathic NPH has not yet been established, and the onset mechanisms and detailed pathomechanisms of NPH are not fully understood. Here, we demonstrate a high spontaneous prevalence (34.6%) of hydrocephalus without clinical symptoms in inbred cotton rats (Sigmodon hispidus). In all 46 hydrocephalic cotton rats, the severity was mild or moderate and not severe. The dilation was limited to the lateral ventricles, and none of the hemorrhage, ventriculitis, meningitis, or tumor formation was found in hydrocephalic cotton rats. These findings indicate that the type of hydrocephalus in cotton rats is similar to that of communicating idiopathic NPH. Histopathological examinations revealed that the inner granular and pyramidal layers (layers IV and V) of the neocortex became thinner in hydrocephalic brains. A small number of pyramidal cells were positive for Fluoro‐Jade C (a degenerating neuron marker) and ionized calcium‐binding adaptor molecule 1 (Iba1)‐immunoreactive microglia were in contact with the degenerating neurons in the hydrocephalic neocortex, suggesting that hydrocephalic cotton rats are more or less impaired projections from the neocortex. This study highlights cotton rats as a candidate for novel models to elucidate the pathomechanism of idiopathic NPH. Additionally, cotton rats have some noticeable systemic pathological phenotypes, such as chronic kidney disease and metabolic disorders. Thus, this model might also be useful for researching the comorbidities of NPH to other diseases.
An autopsy case of adult‐onset neuronal intranuclear inclusion disease with perivascular preservation in cerebral white matter
Authors: Yoshii Daisuke , Ayaki Takashi , Wada Takafumi , Ozaki Akihiko , Yamamoto Toru , Miyagi Yoshimi , Senzaki Hideto , Takahashi Ryosuke
Published: December 2021

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by appearance of eosinophilic hyaline intranuclear inclusions. While the main symptoms of adult‐onset NIID are dementia or limb weakness, some patients present with encephalitic episodes and transient neurological symptoms. The pathophysiology of these acute, transient symptoms, however, remains unknown. Here, we describe an autopsy case of adult‐onset NIID with progressive dementia and transient hemiparesis. The patient was a 70‐year‐old man without a relevant family history, and initially presented with progressive dementia. He then exhibited transient left hemiparesis at 75 years of age and died of ureteral cancer at 77 years of age. Neuropathological examination revealed the presence of multiple areas of focal spongiosis in the subcortical white matter and patchy myelin pallor of the white matter, as in previous reports. However, perivascular areas were preserved even in the damaged white matter. In addition, dense glial fibrillary acidic protein (GFAP)‐immunoreactive astrocytic processes were observed in these areas. [Correction added on 23 January 2022, after first online publication: the preceding sentence has been corrected to improve readability.] GFAP immunohistochemistry revealed decreased density and morphological abnormalities of astrocytes in the affected white matter. These pathological findings might reflect blood–brain barrier impairment and dysregulation of blood flow, which may be related to the pathophysiology of the acute, transient symptoms observed in NIID.
Autoimmune and viral risk factors are associated with achalasia: A case‐control study
Authors: Gaber Charles E. , Cotton Cary C. , Eluri Swathi , Lund Jennifer L. , Farrell Timothy M. , Dellon Evan S.
Published: December 2021

Background

Achalasia is a rare esophageal motility disorder of uncertain etiology. While past studies have indicated that autoimmune conditions and viral infections may be associated with development of achalasia, these associations are yet to be examined in large, population‐based studies.

Methods

A matched case‐control study was performed using administrative claim data from the IBM MarketScan Commercial Claims and Encounters Database between 2000 and 2019. A history of selected autoimmune conditions and viral infections was assessed using past medical claims. Multivariable conditional logistic regression was used to account for the matched nature of the study design and further control for confounding by demographic and clinical characteristics when reporting adjusted odds ratios (aORs).

Key Results

Among 6769 cases and 27,076 controls, presence of any of the autoimmune conditions studied was associated with increased odds of achalasia (aOR = 1.26, 95% CI: 1.11, 1.42). Scleroderma or systemic sclerosis (aOR = 8.13, 95% CI: 3.34, 19.80) and Addison's disease (aOR = 3.83, 95% CI: 1.83, 8.04) had the strongest associations with achalasia. Presence of any of the viral infections studied was also associated with an increased risk of achalasia (aOR = 1.58, 95% CI: 1.23, 2.01). Varicella zoster virus (aOR = 3.84, 95% CI: 1.94, 7.62) and human papillomavirus (aOR = 1.77, 95% CI: 1.15, 2.73) both had strong relationships with achalasia.

Conclusions and Inferences

These findings suggest that achalasia may have autoimmune and viral components contributing to its etiology. Future mechanistic studies could target specific diseases and agents highlighted by this research.
Qing‐Dai for pediatric ulcerative colitis multicenter survey and systematic review
Authors: Kudo Takahiro , Jimbo Keisuke , Shimizu Hirotaka , Iwama Itaru , Ishige Takashi , Mizuochi Tatsuki , Arai Katsuhiro , Kumagai Hideki , Uchida Keiichi , Abukawa Daiki , Shimizu Toshiaki
Published: December 2021

Background

Pediatric ulcerative colitis (UC) is more challenging to treat than adult UC. Qing‐Dai therapy is effective in adults but reports of its efficacy in children are unavailable. We conducted a questionnaire survey on Qing‐Dai use among pediatric patients with UC in Japan to determine its efficacy and safety.

Methods

Questionnaires were sent to 31 high‐volume centers treating pediatric patients with inflammatory bowel disease. The number of patients using Qing‐Dai, short‐term and long‐term effects, and adverse events were assessed. A systematic review of studies on the efficacy and safety of Qing‐Dai usage for UC was also performed.

Results

Overall, 29/31 facilities (93.5%) responded, Qing‐Dai was used in 107 patients with UC, and 84/107 patients (78.5%) initiated treatment. Within 6 months, 81/101 (80.2%) patients had clinical remission, while 59/92 (64.1%) patients had no relapse and 29/92 (31.5%) experienced only one to two relapses yearly. Eighty‐seven percent of the patients underwent regular follow ups for adverse events, among whom one patient was diagnosed with pulmonary arterial hypertension (PAH), five with enteritis, and one with headache. In the systematic review, the clinical remission rate was 50–80%, and PAH was observed in 14 of 1,158 patients (1.2%).

Conclusions

Qing‐Dai is highly effective in treating pediatric UC. However, Qing‐Dai should be administered with caution as it may cause adverse events such as PAH.
Public health nurses fostering self‐help health promotion groups for older people
Authors: Hada Yayoi , Izumi Hisako
Published: December 2021

Objective

Public health nurses foster self‐help groups that are intended to solve health problems and improve the health of older people. This study aims to clarify how public health nurses foster such self‐help groups.

Design

This is a qualitative study that utilizes one‐to‐one semi‐structured interviews.

Sample

The participants comprised 11 full‐time public health nurses who had experience in fostering self‐help groups and had at least 5 years of experience as public health nurses.

Measurements

Interview transcripts were created, and a qualitative analysis was performed inductively.

Results

In total, 33 themes, 14 theme clusters, and four categories were extracted. The categories were as follows: coordinating with relevant occupations and residents to collect community information and solve health problems, organizing classes from health promotion to member‐centered group activities, ensuring group development support and establishing a support system, and supporting leaders behind the scenes.

Conclusions

Public health nurses begin by gathering information about a given community and sharing local health problems with public health authorities and residents. The nurses build trusting partnerships with members and assign appropriate roles to them to better address their problems. Additionally, the nurses provide indirect group support by encouraging leaders as needed.
Building Polyvalent DNA‐Functionalized Anisotropic AuNPs using Poly‐Guanine‐Mediated In‐Situ Synthesis for LSPR‐Based Assays: Case Study on OncomiR‐155
Authors: Borghei Yasaman‐Sadat , Hosseinkhani Saman
Published: December 2021

DNA‐functionalized gold nanoparticles (DNA‐AuNPs) hold great promise for numerous biomedical applications, especially the building of well‐defined nanosystems. Previously reported methods for the preparation of DNA‐AuNPs all rely on the use of DNA‐bearing free thiol or disulfide groups at their 3′/5′ ends. But here we report a novel polyvalent DNA‐AuNPs conjugation approach by in‐situ fast synthesis of AuNPs at the polyguanine (G12) strands. As confirmed by both TEM images and gel electrophoresis analysis, many poly G strand can form an individual anisotropic AuNP and so each AuNP functionalized with a dense layer of DNA, resulting in the formation of polyvalent (p)DNA–AuNPs. The general applicability of this novel approach was further verified in hybridization test and UV‐Vis spectroscopy results show that pDNA–AuNPs conjugation is more attractive in biomedical diagnosis and specific sequence detection like microRNA‐155 by using an extra‐strand poly G with “sticky end” that are complementary to the target sequence.
Retrospective analysis of commercial heterospermic and homospermic cooled boar semen: Effect of the season, sample type and shipping temperature on sperm quality
Authors: Gonzalez‐Castro Raul , Porflidt Carolina , Patton Toni , Goins Donna , Herickhoff Lisa
Published: December 2021

We retrospectively analysed data from heterospermic and homospermic boar semen for motility and morphology during a 2‐year period. Homospermic doses were also evaluated for viability, acrosome integrity, DNA fragmentation, osmolality and pH. Additionally, we investigated the effect of temperature upon arrival and the agreement between viability and motility as evaluating tool. We observed lower (p < .05) total motility (TM) and normal sperm morphology within summer and fall. Conversely, lower (p < .05) progressive motility (PM) was found at the beginning and end of each year. Viability and acrosome integrity were reduced (p < .05) in summer months but not exclusively, suggesting that samples could be compromised by transport temperature. Sperm DNA fragmentation was <6% with a small variation. Medium osmolality and pH slightly changed (p < .05). Sperm count was not source of variation on sperm parameters. Sample temperature upon arrival correlated with PM and VSL (p < .05), while motility was reduced <12°C (p < .05). Homospermic doses were less affected by season and arrival temperature, having better parameters (p < .05) than contemporaneous heterospermic samples but influenced by genetic line (p < .05). We found a high agreement between viable acrosome‐intact sperm and TM, especially when TM was ≥80%. Our data verify the improvement of sperm quality during time as sperm count/dose does not affect quality, but season effect persists regardless of ejaculate selection at the stud. Homospermic doses exhibited better parameters than heterospermic doses, seemingly being more resilient to temperature variations, suggesting that selection for sperm quality within boars selected by growth traits can improve the product quality.
Singled out no longer: The changing narratives and types of single‐parent families
Authors: Yorks Jessica
Published: December 2021

Single parenthood has risen dramatically in the United States over the last 50 years, along with social science research on these families. Some of this early research centered on causes as well as the consequences of single parenthood, especially on children, the latter of which many scholars argue reifies differences as problematic in single‐parent families by comparing them against the “normative” framework of heterosexual, married‐parent families. More recently, however, there has been much growth in social science research that examines the lived experiences of single parents and their children. In this review, I focus on this expanding field of inquiry and present research that highlights the diversity and complexity of single‐parent families. In particular, I summarize the classed, raced, and gendered media and public discourse on single parents, the changing demographics of single parenthood in the United States, and the ways that poor, Black single mothers are shifting the narrative on these families. I also discuss three types of single‐parent families that have received increasing scholarly attention: single parents in multigenerational homes, single fathers, and single parents “by choice.” These subtypes further nuance discussion of single parenthood by highlighting the growing diversity of these families. New developments and future directions for research on single parenthood are also discussed.