bluuebunny/crossref_metadata_2025 huggingface dataset:
Letter: rationalising aminosalicylates in inflammatory bowel disease—authors' reply
Authors: Chapman Thomas P. , Frias Gomes Catarina , Louis Edouard , Colombel Jean‐Frédéric , Satsangi Jack
Published: September 2023

LINKED CONTENT

This article is linked to Chapman et al and Nicolaides et al papers. To view these articles, visithttps://doi.org/10.1111/apt.15771andhttps://doi.org/10.1111/apt.16107
Real‐world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate‐treated chronic hepatitis B pregnant patients in North America
Authors: Samadi Kochaksaraei Golasa , Castillo Eliana , Sadler Matthew D. , Seow Cynthia H.‐T. , Barkema Herman W. , Martin Steven R. , Israelson Heidi , Pinto Jacqueline , Williams Sarah , Aspinall AIexander I. , Stinton Laura M. , Borman Meredith A. , Burak Kelly W. , Swain Mark G. , Congly Stephen E. , Lee Samuel S. , Shaheen Abdel Aziz , Coffin Carla S.
Published: September 2023

Background

There are limited long‐term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)‐treated women during pregnancy.

Aims

To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post‐partum in a low HBV endemic region.

Methods

Retrospective real‐world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post‐partum.

Results

In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7‐39.5) post‐partum, 19% (65/341) received TDF (11 initiated pre‐pregnancy, 53 for mother‐to‐child transmission (MTCT) prevention). During follow‐up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re‐treated. In all TDF‐treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow‐up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post‐partum, requiring re‐treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post‐partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post‐partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23‐40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12‐26) post‐partum.

Conclusions

Post‐partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long‐term follow‐up.
Letter: synergistic role of gut flora with aspirin to prevent colorectal cancers—authors’ reply
Authors: Prizment Anna E. , Onyeaghala Guillaume C. , Church Timothy R.
Published: September 2023

LINKED CONTENT

This article is linked to Prizment et al and Li et al papers. To view these articles, visit https://doi.org/10.1111/apt.16013 and https://doi.org/10.1111/apt.16093
Histologic remission does not offer additional benefit for ulcerative colitis patients in endoscopic remission
Authors: Narula Neeraj , Aruljothy Achuthan , Alshahrani Abdul‐Aziz , Fadida Ma’ayan , Al‐Saedi Mona , Marshall John K. , Rubin David T. , Christensen Britt
Published: September 2023

Background

Histologic remission in ulcerative colitis (UC) patients may be associated with positive outcomes. It is unclear whether UC patients in endoscopic remission obtain additional benefit from achieving histologic remission.

Aim

To evaluate the relationship between time to relapse and histological activity among UC patients in endoscopic remission.

Methods

In this retrospective study using an observational database, we identified UC patients who had achieved endoscopic remission (Mayo endoscopic subscore 0). Index colonoscopy was the first colonoscopy when endoscopic remission was achieved. Histologic activity was classified as normal, inactive or active colitis. The primary outcome was time to relapse. Secondary outcomes included reasons for relapse and the association between baseline variables and risk of relapse. A Cox proportional hazards model evaluated baseline factors and the outcome of relapse.

Results

We included 269 patients. The Kaplan‐Meier survival curve showed no significant difference between the presence or absence of histologic activity and time to relapse (log rank P = 0.85). There was no difference in time to clinical relapse of patients with histologically active colitis compared to inactive colitis (adjusted hazard ratio [AHR] 1.17, 95% CI 0.58‐2.32, P = 0.67]). 5‐aminosalicylate use (AHR 0.42, 95% CI 0.21‐0.82, P = 0.011), pancolitis (AHR 0.32, 95% CI 0.13‐0.75, P = 0.008), left‐sided colitis (AHR 0.46; 95% CI 0.22‐0.98; P = 0.044) and older age (AHR 0.96, 95% CI 0.94‐0.99, P = 0.002) were significantly associated with reduced time to clinical relapse.

Conclusion

Histologic remission did not influence time to relapse in UC patients who had achieved endoscopic remission.
The role of identity‐related beliefs in the appraisal and management of crowding: Insights from the Hajj
Authors: Yalcin Enes , Hopkins Nick
Published: September 2023

In crowds, to the degree one identifies with other crowd members one likely experiences a sense of common purpose, social connection and mutual support. Such is the psychological significance of these correlates of a shared identity that even others' close physical proximity can be pleasurable. However, such pleasure in others' proximity cannot be assumed: physical crowding can bring practical challenges and so potentially disturb the positive experience of crowd membership. In the research reported here, we explore crowd members' reports of such challenges and the ways in which these were interpreted and managed through reference to the beliefs and values associated with crowd members' shared identity. Our data arise from semi‐structured interviews (N = 33) with British Muslims after participating in the Hajj pilgrimage in Saudi Arabia. Exploring these data sheds light on the ways in which identity‐related beliefs and values can contribute to the maintenance of order and harmony even in situations where crowding could undermine the positive experience of others' proximity. Accordingly, our analysis advances our understanding of the self‐organization and self‐policing of crowds.
B7H3 increases ferroptosis resistance by inhibiting cholesterol metabolism in colorectal cancer
Authors: Jin Haiyan , Zhu Mengxin , Zhang Dongze , Liu Xiaoshan , Guo Yuesheng , Xia Lu , Chen Yanjun , Chen Yuqi , Xu Ruyan , Liu Cuiping , Xi Qinhua , Xia Suhua , Shi Tongguo , Zhang Guangbo
Published: September 2023

Ferroptosis, a newly discovered form of regulated cell death, has been reported to be associated with multiple cancers, including colorectal cancer (CRC). However, the underlying molecular mechanism is still unclear. In this study, we identified B7H3 as a potential regulator of ferroptosis resistance in CRC. B7H3 knockdown decreased but B7H3 overexpression increased the ferroptosis resistance of CRC cells, as evidenced by the expression of ferroptosis‐associated genes (PTGS2, FTL, FTH, and GPX4) and the levels of important indicators of ferroptosis (malondialdehyde, iron load). Moreover, B7H3 promoted ferroptosis resistance by regulating sterol regulatory element binding protein 2 (SREBP2)‐mediated cholesterol metabolism. Both exogenous cholesterol supplementation and treatment with the SREBP2 inhibitor betulin reversed the effect of B7H3 on ferroptosis in CRC cells. Furthermore, we verified that B7H3 downregulated SREBP2 expression by activating the AKT pathway. Additionally, multiplex immunohistochemistry was carried out to show the expression of B7H3, prostaglandin‐endoperoxide synthase 2, and SREBP2 in CRC tumor tissues, which was associated with the prognosis of patients with CRC. In summary, our findings reveal a role for B7H3 in regulating ferroptosis by controlling cholesterol metabolism in CRC.
Berberine derivatives as inhibitors of acetylcholinesterase: A systematic review
Authors: Singh Yash Pal , Kumar Harish
Published: September 2023

Alzheimer's disease (AD) is a chronic age‐related neurodegenerative brain disorder characterized by the impairment of memory accompanied by worsening of thinking ability of an individual. The exact pathophysiology of AD is not fully understood. However low level of the neurotransmitter named acetylcholine (ACh), aggregation of Aβ peptide into toxic Aβ plaque, hyperphosphorylation of tau, bio‐metal imbalance, and oxidative stress are the main hallmarks of this disease. Due to the complex pathophysiology of AD, no specific treatment is available in the market, and treatment is only limited to the symptomatic relief. So, there is an urgent need for the development of new drug candidate, which can have disease‐modifying effect and improve learning and memory in AD patient. Therefore, berberine‐based multifunction compounds with potential cholinesterase inhibitory properties were reviewed in this article. Structure–activity relationship (SAR) and biological activity provide highlights on the new derivatives used for the management of AD.
Formalizing developmental phenomena as continuous‐time systems: Relations between mathematics and language development
Authors: Driver Charles C. , Tomasik Martin J.
Published: September 2023

We demonstrate how developmental theories may be instantiated as statistical models, using hierarchical continuous‐time dynamic systems. This approach offers a flexible specification and an often more direct link between theory and model parameters than common modeling frameworks. We address developmental theories of the relation between the academic competencies of mathematics and language, using data from the online learning system Mindsteps. We use ability estimates from 160,164 observation occasions, across N = 4623 3rd to 9th grade students and five ability domains. Model development is step‐by‐step from simple to complex, with ramifications for theory and modeling discussed at each step.
Selective HDAC6 inhibition protects against blood–brain barrier dysfunction after intracerebral hemorrhage
Authors: Peng Cuiying , Wang Yilin , Hu Zhiping , Chen Chunli
Published: September 2023

Backgrounds

Blood–brain barrier (BBB) disruption after intracerebral hemorrhage (ICH) significantly induces neurological impairment. Previous studies showed that HDAC6 knockdown or TubA can protect the TNF‐induced endothelial dysfunction. However, the role of HDAC6 inhibition on ICH‐induced BBB disruption remains unknown.

Methods

Hemin‐induced human brain microvascular endothelial cells (HBMECs) and collagenase‐induced rats were employed to investigated the underlying impact of the HDAC6 inhibition in BBB lesion and neuronal dysfunction after ICH.

Results

We found a significant decrease in acetylated α‐tubulin during early phase of ICH. Both 25 or 40 mg/kg of TubA could relieve neurological deficits, perihematomal cell apoptosis, and ipsilateral brain edema in ICH animal model. TubA or specific siRNA of HDAC6 inhibited apoptosis and reduced the endothelial permeability of HBMECs. HDAC6 inhibition rescued the degradation of TJ proteins and repaired TJs collapses after ICH induction. Finally, the results suggested that the protective effects on BBB after ICH induction were exerted via upregulating the acetylated α‐tubulin and reducing stress fiber formation.

Conclusions

Inhibition of HDAC6 expression showed beneficial effects against BBB disruption after experimental ICH, which suggested that HDAC6 could be a novel and promising target for ICH treatment.
Participation of the nucleus tractus solitarius in the therapeutic effect of electroacupuncture on post‐stroke dysphagia through the primary motor cortex
Authors: Ye Qiuping , Yuan Si , Yao Lulu , Dai Yong , Deng Bing , Hu Jiahui , Qiao Jiao , Wen Hongmei , Dou Zulin , Xu Nenggui
Published: September 2023

Background

Post‐stroke dysphagia (PSD), a common and serious disease, affects the quality of life of many patients and their families. Electroacupuncture (EA) has been commonly used effectively in the treatment of PSD, but the therapeutic mechanism is still under exploration at present. We aim to investigate the effect of the nucleus tractus solitarus (NTS) on the treatment of PSD by EA at Lianquan (CV23) through the primary motor cortex (M1).

Methods

C57 male mice were used to construct a PSD mouse model using photothrombotic technique, and the swallowing function was evaluated by electromyography (EMG) recording. C‐Fos‐positive neurons and types of neurons in the NTS were detected by immunofluorescence. Optogenetics and chemical genetics were used to regulate the NTS, and the firing rate of neurons was recorded via multichannel recording.

Results

The results showed that most of the activated neurons in the NTS were excitatory neurons, and multichannel recording indicated that the activity levels of both pyramidal neurons and interneurons in the NTS were regulated by M1. This process was involved in the EA treatment. Furthermore, while chemogenetic inhibition of the NTS reduced the EMG signal associated with the swallowing response induced by activation of M1 in PSD mice, EA rescued this signal.

Conclusion

Overall, the NTS was shown to participate in the regulation of PSD by EA at CV23 through M1.
A case of cutaneous malignant glomus tumor
Authors: Senff Sebastian , Orschulok Thomas P. , Lambie Duncan L. , Lehane Fiona
Published: September 2023

Glomus tumors are well‐known but relatively rare vascular neoplasms, with their malignant counterparts still being rarer. There are very few reports of cutaneous malignant glomus tumors, and the current limited evidence suggests that they follow a more indolent course than deep‐seated malignant glomus tumors. Herein, we are reporting a case of cutaneous malignant glomus tumor. A 94‐year‐old male presented with a right‐sided ulcerated scalp lesion, which, on biopsy, showed a diffusely infiltrative epithelioid malignancy with considerable pleomorphism and a notable perivascular growth pattern. The tumor cells were positive for smooth muscle actin (SMA) and h‐caldesmon, and negative for cytokeratin MNF116, CK5, p40, S100, SOX10, HMB45, Melan‐A, ERG, CD31, CD45, CD3, CD20, ALK, desmin, CD68, CD34, and HHV8. A diagnosis of cutaneous malignant glomus tumor was made, and the patient underwent a wider excision. Cutaneous malignant glomus tumors are extremely rare and should be considered when examining unusual cutaneous mesenchymal tumors.
A case of lymphomatous pleural effusion from angioimmunoblastic T‐cell lymphoma: The methodology of cell transfer technique and immunocytochemistry on an inadequate cytology specimen can potentially guide us to the correct diagnosis
Authors: Takebayashi Kinue , Kadoguchi Rie , Shioya Akihiro , Oyama Takeru , Yamada Sohsuke
Published: September 2023

The cytological diagnosis of lymphomatous pleural effusion from AITL was difficult to make, due to the insufficient/inadequate volume of the submitted specimen with a very small number of atypical immature medium‐to‐large lymphoid cells. However, the methodology of cell transfer technique and immunocytochemistry can potentially guide us to the correct cytological diagnosis.
Impact of body size on critical thermal maxima in female solitary desert bees
Authors: Barrett M. , Tigreros N. , Davidowitz G. , O'Donnell S.
Published: September 2023

Solitary, size‐variable bees are adapted to a wide range of thermal environments (e.g., through critical thermal maxima, or CTmax) and are important, understudied subjects for research on species' vulnerability to climate change.

Centris pallida are solitary, ground‐nesting desert bees with females varying two‐fold in body mass. We hypothesized that body size would affect CTmax in female C. pallida, predicting that an increase in body size would result in increased thermal tolerance.

We tested the effects of female body mass on CTmax using a ramping CTmax assay while controlling for age. We used flow‐through respirometry to confirm that the behavioural indicator of CTmax correlated with the metabolic indicator of lethality.

Body mass correlated positively with CTmax; every 100 mg increase in body mass resulted in a 1.5°C increase in CTmax.

Female age (as assessed by an index score based on wing, thorax hair and mandibular wear) did not affect CTmax.

Flow‐through respirometry confirmed that loss of muscle control correlated with the metabolic ‘mortal fall’, or a decline in CO2 production.

As insect body sizes typically decline with higher temperatures, our data suggest rising temperatures could magnify thermal stresses on desert bee populations.
A loss‐of‐function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa
Authors: de Oliveira Ana Sofia Lima Estevao , de Siqueira Roberta Cardoso , Nait‐Meddour Cécile , Tricarico Paola Maura , Moura Ronald , Agrelli Almerinda , d'Adamo Adamo Pio , Jamain Stéphane , Crovella Sergio , de Fátima Medeiros Brito Maria , Boniotto Michele , Brandão Lucas André Cavalcanti
Published: September 2023

Dowling Degos disease (DDD) is a rare autosomal dominant genodermatosis characterized by acquired, slowly progressive reticulated pigmented lesions primarily involving flexural skin areas. Mutations in KRT5, POGLUT‐1 and POFUT‐1 genes have been associated with DDD, and loss‐of‐function mutations in PSENEN, a subunit of the gamma‐secretase complex, were found in patients presenting with DDD or DDD comorbid with hidradenitis suppurativa (HS). A nonsense mutation in NCSTN, another subunit of the gamma‐secretase, was already described in a patient suffering from HS and DDD but whether NCSTN could be considered a novel gene for DDD is still debated. Here, we enrolled a four‐generation family with HS and DDD. Through Whole Exome Sequencing (WES) we identified a novel nonsense mutation in the NCSTN gene in all the affected family members. To study the impact of this variant, we isolated outer root sheath cells from patients' hair follicles. We showed that this variant leads to a premature stop codon, activates a nonsense‐mediated mRNA decay, and causes NCSTN haploinsufficiency in affected individuals. In fact, cells treated with gentamicin, a readthrough agent, had the NCSTN levels corrected. Moreover, we observed that this haploinsufficiency also affects other subunits of the gamma‐secretase complex, possibly causing DDD. Our findings clearly support NCSTN as a novel DDD gene and suggest carefully investigating this co‐occurrence in HS patients carrying a mutation in the NCSTN gene.
Adenosine monophosphate‐regulated protein kinase inhibition modulates electrophysiological characteristics and calcium homeostasis of rabbit right ventricular outflow tract
Authors: Lu Yen‐Yu , Cheng Chen‐Chuan , Chen Yao‐Chang , Lin Yung‐Kuo , Higa Satoshi , Kao Yu‐Hsun , Chen Yi‐Jen
Published: September 2023

Background

Metabolic stress predisposes to ventricular arrhythmias and sudden cardiac death. Right ventricular outflow tract (RVOT) is the common origin of ventricular arrhythmias. Adenosine monophosphate‐regulated protein kinase (AMPK) activation is an important compensatory mechanism for cardiac remodeling during metabolic stress.

Objectives

The purpose of this study was to access whether AMPK inhibition would modulate RVOT electrophysiology, calcium (Ca2+) regulation, and RVOT arrhythmogenesis or not.

Methods

Conventional microelectrodes were used to record electrical activity before and after compound C (10 µM, an AMPK inhibitor) in isoproterenol (1 µM)‐treated rabbit RVOT tissue preparations under electrical pacing. Whole‐cell patch‐clamp and confocal microscopic examinations were performed in baseline and compound C‐treated rabbit RVOT cardiomyocytes to investigate ionic currents and intracellular Ca2+ transients in isolated rabbit RVOT cardiomyocytes.

Results

Compound C decreased RVOT contractility, and reversed isoproterenol increased RVOT contractility. Compound C decreased the incidence, rate, and duration of isoproterenol‐induced RVOT burst firing under rapid pacing. Compared to baseline, compound C‐treated RVOT cardiomyocytes had a longer action potential duration, smaller intracellular Ca2+ transients, late sodium (Na+), peak L‐type Ca2+ current density, Na+‐Ca2+ exchanger, transient outward potassium (K+) current, and rapid and slow delayed rectifier K+ currents.

Conclusion

AMPK inhibition modulates RVOT electrophysiological characteristics and Ca2+ homeostasis, contributing to lower RVOT arrhythmogenic activity. Accordingly, AMPK inhibition might potentially reduce ventricular tachyarrhythmias.
Climate genomics—Geoscientists, ecologists, and geneticists must reinforce their collaborations to confront climate change
Authors: Caccavo Jilda Alicia , Frémont Paul , Jaillon Olivier , Gehlen Marion
Published: September 2023

Geoscientists and ecologists alike must confront the impact of climate change on ecosystems and the services they provide. In the marine realm, major changes are projected in net primary and export production, with significant repercussions on food security, carbon storage, and climate system feedbacks. However, these projections do not include the potential for rapid linear evolution to facilitate adaptation to environmental change. Climate genomics confronts this challenge by assessing the vulnerability of ecosystem services to climate change. Because DNA is the primary biological repository of detectable environmentally selected mutations (showing evidence of change before impacts arise in morphological or metabolic patterns), genomics provides a window into selection in response to climate change, while also recording neutral processes deriving from stochastic mechanisms (Lowe et al., Trends in Ecology & Evolution, 2017; 32:141–152). Due to the revolution afforded by sequencing technology developments, genomics can now meet ecologists and climate scientists in a cross‐disciplinary space fertile for collaborations. Collaboration between geoscientists, ecologists, and geneticists must be reinforced in order to combine modeling and genomics approaches at every scale to improve our understanding and the management of ecosystems under climate change. To this end, we present advances in climate genomics from plankton to larger vertebrates, stressing the interactions between modeling and genomics, and identifying future work needed to develop and expand the field of climate genomics.
How well do participatory governance arrangements serve political leadership?
Authors: Winsvold Marte , Vabo Signy Irene
Published: September 2023

Participatory governance arrangements are assumed to strengthen elected representatives' capacity for political leadership. This study argues that the relationship between participatory arrangements and perceived political leadership depends on the design of the participatory arrangements. Drawing on a survey to local councilors in Norway, we found that sharing power with citizens through interactive governance arrangements was associated with lower perceived capacity for political leadership than giving power away through distributive arrangements. Case studies exploring how politicians experienced interactive and distributive participatory arrangements showed that politicians were especially ambivalent about interactive arrangements that were perceived to disrupt their traditional ways of doing political leadership. Notably, interactive arrangements were believed to decrease leadership capacity because politicians remained responsible for matters over which they no longer had full control, challenging their ability to stay accountable to the voters.
Knowledge and acceptance of malaria vaccine among parents of under‐five children of malaria endemic areas in Bangladesh: A cross‐sectional study
Authors: Amin Mohammad Ashraful , Afrin Sadia , Bonna Atia S. , Rozars Md Faisal K. , Nabi Mohammad Hayatun , Hawlader Mohammad Delwer H.
Published: September 2023

Background

Malaria exists as an endemic in many countries including Bangladesh and the malaria vaccine is not yet available here. The study aimed to assess the level of knowledge and acceptance of the malaria vaccination among the parents of children under the age of five in Bangladesh's malaria‐endemic areas and the sociodemographic, behavioural, and household factors associated with the acceptance and knowledge of the malaria vaccine.

Methods

From January to March 2022, a cross‐sectional study was conducted in all five malaria‐endemic districts of Bangladesh, involving 405 parents of children under the age of 5 who met the inclusion criteria. Multiple logistic regression was used to analyze the factor affecting parents' acceptance and knowledge of malaria vaccination in children under five and other variables.

Results

Majority (54%) of the respondents were mothers. Almost half (49%) of the respondents were aged between 26 and 35 years old and around 90% were from rural areas. A small portion (20%) of the participants were housewives and 46% of them completed primary education. Overall, 70% of the study participants reported that they would accept malaria vaccination independently. About one‐fourth (25%) heard about the malaria vaccine and 48% of them mentioned health professionals as the source of information. Knowledge of malaria vaccination was found associated with residence, income, and family size. Acceptance and knowledge were both associated with residence, education, occupation, income, and family size. In a multivariable analysis, housing structure, house wall, house window, knowledge of malaria, testing for malaria, and being diagnosed with malaria were all associated with knowledge of and acceptance of getting vaccinated against malaria.

Conclusions

The present study highlights the necessity of creating awareness of malaria vaccines in epidemic areas of Bangladesh. This study offers crucial data to develop a policy for a novel malaria vaccine, supporting its adoption in Bangladesh.

Public Contribution

This study was based on interviews. The interviewees were recruited as public representatives from the malaria‐endemic area to assist us in building an understanding of knowledge and acceptance of the malaria vaccine among parents of under‐five children in Bangladesh.
Metallothionein: a game changer in histopathological diagnosis of Wilson disease
Authors: Wiethoff Hendrik , Mohr Isabelle , Fichtner Alexander , Merle Uta , Schirmacher Peter , Weiss Karl H , Longerich Thomas
Published: September 2023

Aims

Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations in the ATP7B gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric disorders with variable presentation. Metallothionein (MT) immunohistochemistry was proposed as a diagnostic marker.

Methods

MT immunohistochemistry was performed on liver specimens of WD patients (n = 64) and control cases (n = 160) including acute liver failure, steatotic liver disease, autoimmune hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff for detection of WD was determined by receiver operating characteristic (ROC) analysis.

Results

At least moderate staining in >50% of hepatocytes was observed in 81% of analysed liver specimens (n = 56/69) of WD patients, while only five control cases showed this staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients was 70.6% and this MT pattern was robust in small biopsies. The hepatic copper concentration was similar between MT‐positive and MT‐negative liver samples (P > 0.05). Zinc treatment may induce hepatocellular MT expression. Kayser–Fleischer rings (50% versus 15%) and neurologic disorders (50% versus 13%) were significantly more prevalent in MT‐negative compared to MT‐positive WD patients, respectively.

Conclusion

MT immunostaining is an excellent biomarker for histological diagnosis of WD, should be incorporated in the diagnostic work‐up of patients with potential WD, and is useful in a modified Leipzig score.
Effect of two shampoo formulations on the prokaryotic and eukaryotic microbiota composition of the human scalp
Authors: Jacksch Susanne , Weis Severin , März Melanie , Gruedl Sabine , Simmering Rainer , Welss Thomas , Egert Markus
Published: September 2023

Objective

The human scalp is characterized by a moderately diverse microbial community, comprising prokaryotic (bacteria) and eukaryotic (fungi) members. Although the details are far from being fully understood, the human scalp microbiota is implicated in several scalp disorders, in particular dandruff formation. Hence, the protection of an intact and diverse scalp microbiota can be regarded as a quality criterion for hair and scalp care formulations. In this study, we investigated the influence of two commercially available, non‐antimicrobial shampoo formulations on the structure of the scalp microbiota.

Methods

Scalp microbiota samples, obtained by swab sampling from two cohorts of probands (n = 25, each), were analysed before and after daily use of two different shampoo formulations for 2 weeks, respectively. A polyphasic approach was used, comprising quantitative cultivation of bacteria and fungi on selective media as well as sequencing of PCR‐amplified 16S rRNA and 18S rRNA genes, respectively.

Results

All analyses revealed a microbiota composition typical for the human scalp. While in particular fungal germ numbers increased significantly during the treatments, overall bacterial and fungal community composition was not affected, based on alpha‐ and beta‐diversity measures. However, we observed an increase in structural bacterial diversity with the age of the probands.

Conclusions

Over an application period of 2 weeks, the investigated shampoo induced quantitative but no qualitative changes in the scalp microbial community structure of the investigated probands, suggesting no adverse but rather preserving or even stimulating effects of the underlying formulations on the scalp microbiota. Further investigation will have to clarify if this is also true for longer application periods and if the formulations might affect community functionality, for example microbial gene expression, rather than community composition.
Association of monoclonal gammopathy of undetermined significance and C3 glomerulopathy
Authors: Ekladious Adel , Bhandari Ritesh , Javaid Muhammad M.
Published: September 2023

Monoclonal gammopathy of undetermined significance (MGUS) is usually an asymptomatic pre‐malignant condition caused by the proliferation of clonal plasma cells. Often considered a benign condition, it has the potential to progress to malignant plasma cell or lymphoproliferative disorders. Moreover, MGUS can rarely cause glomerular disease by activating the alternative complement pathway resulting in immunoglobulin‐negative C3‐positive glomerulonephritis called C3 glomerulopathy. Because of its rarity, the diagnosis might not be considered by the treating physicians, leading to delayed diagnosis or misdiagnosis. Untreated C3 glomerulopathy can lead to irreversible glomerular damage and end‐stage renal failure, and a high index of suspicion is essential for timely diagnosis and management. Here, we present the case of a patient with a prior diagnosis of MGUS who presented with proteinuria and microscopic haematuria and was diagnosed with C3 glomerulopathy. The patient had complete resolution of the disease after receiving treatment with a combination of dexamethasone, lenalidomide and bortezomib for the underlying MGUS.
Dehydrated human amnion/chorion membrane allograft with spongy layer to significantly improve the outcome of chronic non‐healing wounds
Authors: Psathas Emmanouil , Egger Bernhard , Mayer Dieter
Published: September 2023

We investigated the healing effect of a new dehydrated amnion/chorion membrane with a spongy layer over a 30‐month period in 32 patients with 53 chronic non‐healing wounds of different aetiologies. Wounds with <40% surface reduction after 4 weeks of best wound treatment underwent weekly allograft application by a certified wound specialist based on national guidelines and a standardised protocol until complete healing or definite treatment interruption. The main outcome measure was the percentage of wound surface reduction from baseline calculated using digital planimetry follow‐up photographs. Overall, 38 (71.7%) wounds presented a favourable outcome (70%–100% area reduction), with 35 (66%) completely healing over a median time of 77 days (range 29–350 days). Favourable outcomes were observed in 75% of traumatic wounds, surgical wounds, venous leg ulcers and pressure injuries, as well as in 50% of ischaemic wounds. Wounds being present <12 months were significantly more likely to have a favourable outcome than more long‐standing wounds (χ2 = 7.799; p = 0.005; OR = 3.378; 95% CI, 1.410–8.092). Thus, treatment with dehydrated amnion/chorion membrane with a spongy layer improves the outcome of non‐healing wounds of different aetiologies and, therefore, has to be considered early in the management of refractory wounds.
Investigation of morbidity, length of stay, and healthcare costs of inpatient paediatric burns
Authors: Sari Hıdır , Akkoc Mehmet Fatih , Kilinç Zehra , Dayanir Çok Fatma Nur , Özel Mehmet , Özel Volkan
Published: September 2023

Burn injuries are the third most common cause of death in children due to trauma. Hospitalizations related to burn injuries are common. Prolonged hospitalization associated with burn treatment can result in increased resource utilization, leading to higher costs. Thus, it is essential to investigate these areas to reduce costs. The study investigated the morbidity and length of hospital stay of paediatric burn patients, as well as calculated the social security costs of hospitalization and treatment. The retrospective observational descriptive study examined the medical records of 774 paediatric patients treated in a burn intensive care unit at a tertiary medical faculty hospital between 01 March 2019 and 31 March 2022. The invoice records of payments made by the Social Security Institution to the hospital in return for health services provided to patients were examined. The healthcare costs were calculated. A total of 57.6% of the participants were boys and 79.2% were between the ages of 1–4. About 90% of the cases involved burns with a total body surface area (TBSA) of less than 20% and a 2nd‐degree burn depth. Scalding was the most common cause of burns (88.2%). Among all patients, the mortality rate was 2.1% (n = 16). The mean length of hospital stay was 10.29 ± 9.59 days. The mean cost per day was 212.02 ± 190.94 US dollars ($US), and the cost per 1% TBSA was 241.70 ± 301.32 $US. According to the causes of burn injury, the mean cost of electricity was 5000.77 ± 8101.85 $US, fire 4818.02 ± 5852.22 $US, and chemical 3285.49 ± 4503.2 $US were observed in the first 3 ranks respectively. According to this study, paediatric burn cases occur due to preventable causes, and even though the mortality rate was low, the severity of burns, TBSA%, and presence of complications caused prolonged lengths of hospital stays, which caused social security costs to rise.
Strength retention of single‐phase high‐entropy diboride ceramics up to 2000°C
Authors: Feng Lun , Fahrenholtz William G. , Hilmas Gregory E. , Zhou Yue , Bai Jincheng
Published: September 2023

The mechanical properties of single‐phase (Hf0.2,Nb0.2,Ta0.2,Ti0.2,Zr0.2)B2 ceramics with high purity were investigated. The resulting ceramics had relative density greater than 99%, and an average grain size of 4.3 ± 1.6 μm. At room temperature (RT), the Vickers hardness was 25.2 ± 0.6 GPa at a load of 0.49 N, Young's modulus was 551 ± 7 GPa, fracture toughness was 4.5 ± 0.4 MPa m1/2, and flexural strength was 507 ± 10 MPa. Flexural strength increased by more than 50% from 507 ± 10 MPa at RT to 776 ± 26 MPa at 1400°C. Strength remained above 750 MPa up to 2000°C, but decreased to 672 ± 18 MPa at 2100°C and the bars deformed during testing. No significant changes in residual porosity, average grain size, or oxide impurity levels were observed after testing at elevated temperatures. The increase in strength at elevated temperatures was attributed to healing of microcracks due to thermal expansion at high temperatures, and dislocation formation. The retention of strength up to 2000°C is presumably due to the lack of oxide impurities in the HEBs. This is the first reported study on the flexural strength up to 2100°C of dense and pure HEB ceramics.
Economic policy uncertainty and corporate divestitures
Authors: Frye Melissa B. , Pham Duong T. , Whyte Ann Marie
Published: September 2023

We examine the impact of economic policy uncertainty (EPU) on the propensity of firms to engage in divestitures. We find that EPU is positively related to the likelihood of divestitures in general and cashflow‐generating divestitures in particular. Consistent with the desire for cash being a driving force behind divestitures, we find that underperforming firms are more likely to engage in cashflow‐increasing divestitures. Firms that do not pay dividends and are relatively more reliant on government funding are also more likely to pursue sell‐offs and carve‐outs when economic uncertainty is elevated. We find no evidence that firms prefer staged divestitures (spin‐offs and carve‐outs) over non‐staged (sell‐offs) when EPU is high. Instead, EPU is positively related to the likelihood of non‐staged divestitures suggesting that firms do not wait until uncertainty is resolved to pursue deals with a high degree of irreversibility. Our findings point to EPU as a motivator for poor‐performing firms to shore up cash during times of EPU.
Polydatin alleviates bleomycin‐induced pulmonary fibrosis and alters the gut microbiota in a mouse model
Authors: Yang Jia , Shi Xiawei , Gao Rundi , Fan Liming , Chen Ruilin , Cao Yu , Xu Tingzhen , Yang Junchao
Published: September 2023

To investigate the effect and mechanism of polydatin on bleomycin (BLM)‐induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF‐α, LPS, IL‐6 and IL‐1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α‐diversity, β‐diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx‐induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM‐treated or untreated ABx mice. The histopathological changes and collagen I and α‐SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM‐induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin‐treated BLM mice effectively alleviated lung fibrosis in BLM‐treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM‐induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.
Glucose dysregulation promotes oncogenesis in human bladder cancer by regulating autophagy and YAP1/TAZ expression
Authors: Li Shi , Ruan Banzhan , Wang Zhi , Xia Jianling , Lin Qi , Xu Ruoting , Zhu Hua , Yu Zhixian
Published: September 2023

Glucose dysregulation is strongly correlated with cancer development, and cancer is prevalent in patients with Type 2 diabetes (T2D). We aimed to elucidate the mechanism underlying autophagy in response to glucose dysregulation in human bladder cancer (BC). 220 BC patients were included in this retrospective study. The expression of YAP1, TAZ and AMPK, EMT‐associated markers, and autophagy marker proteins was analysed by immunohistochemistry, western blotting, and quantitative real‐time PCR (qPCR). Further, T24 and UMUC‐3 BC cells were cultured in media with different glucose concentrations, and the expression of YAP1, TAZ, AMPK and EMT‐associated markers, and autophagy marker proteins was analysed by western blotting and qPCR. Autophagy was observed by immunofluorescence and electron microscopy. BC cell viability was tested using MTT assays. A xenograft nude mouse model of diabetes was used to evaluate tumour growth, metastasis and survival. A poorer pathologic grade and tumour‐node‐metastasis stage were observed in patients with BC with comorbid T2D than in others with BC. YAP1 and TAZ were upregulated in BC samples from patients with T2D. Mechanistically, high glucose (HG) promoted BC progression both in vitro and in vivo and inhibited autophagy. Specifically, various autophagy marker proteins and AMPK were negatively regulated under HG conditions and correlated with YAP1 and TAZ expression. These results demonstrate that HG inhibits autophagy and promotes cancer development in BC. YAP1/TAZ/AMPK signalling plays a crucial role in regulating glucose dysregulation during autophagy. Targeting these effectors exhibits therapeutic significance and can serve as prognostic markers in BC patients with T2D.
USF1 regulated circPRDM4 modulates tumorigenesis and immune escape in chemoresistant cervical cancer
Authors: Zhang Yan , Li Xing , Zhang Jun , Mao Lin , Wen Zou , Cao Mingliang , Mu Xuefeng
Published: September 2023

Cervical cancer (CC) represents a major global health concern, characterized by chemoresistance and immune evasion mechanisms. Circular RNAs (circRNAs), which play a crucial role in cancer pathogenesis, particularly in the case of CC, have gained significant attention. The primary objective of this study was to investigate the functional significance of circRNAs in chemoresistant CC. A significant upregulation of circPRDM4 expression in chemoresistant CC cells. To investigate the functional consequences, we conducted circPRDM4 knockdown experiments, which resulted in the effective blockade of immune escape mechanisms employed by chemoresistant CC cells. Furthermore, circPRDM4 knockdown demonstrated a significant suppression of tumorigenesis in CC cells, highlighting its contribution to the oncogenic potential of CC. Investigating the regulatory mechanisms involved, we found that the transcriptional factor upstream stimulatory factor 1 (USF1) acts as an inducer of circPRDM4 expression. Remarkably, USF1 was found to effectively modulate CC cell immune escape via its interaction with circPRDM4. Moreover, our results revealed that USF1 is intricately involved in CC cell tumorigenesis through the regulation of circPRDM4. Collectively, our study elucidates the significant roles of circPRDM4 and its upstream regulator USF1 in chemoresistant CC cells. These findings underscore the importance of circRNAs in CC pathogenesis and provide valuable insights into the mechanisms underlying immune escape and tumorigenesis.
The SlWRKY57‐SlVQ21/SlVQ16 module regulates salt stress in tomato
Authors: Ma Jilin , Li Chonghua , Sun Lulu , Ma Xuechun , Qiao Hui , Zhao Wenchao , Yang Rui , Song Susheng , Wang Shaohui , Huang Huang
Published: September 2023

Salt stress is a major abiotic stress which severely hinders crop production. However, the regulatory network controlling tomato resistance to salt remains unclear. Here, we found that the tomato WRKY transcription factor WRKY57 acted as a negative regulator in salt stress response by directly attenuating the transcription of salt‐responsive genes (SlRD29B and SlDREB2) and an ion homeostasis gene (SlSOS1). We further identified two VQ‐motif containing proteins SlVQ16 and SlVQ21 as SlWRKY57‐interacting proteins. SlVQ16 positively, while SlVQ21 negatively modulated tomato resistance to salt stress. SlVQ16 and SlVQ21 competitively interacted with SlWRKY57 and antagonistically regulated the transcriptional repression activity of SlWRKY57. Additionally, the SlWRKY57‐SlVQ21/SlVQ16 module was involved in the pathway of phytohormone jasmonates (JAs) by interacting with JA repressors JA‐ZIM domain (JAZ) proteins. These results provide new insights into how the SlWRKY57‐SlVQ21/SlVQ16 module finely tunes tomato salt tolerance.
Scale of Emotional Development – Short: reliability and validity in adults with intellectual disability
Authors: Flachsmeyer M. , Sterkenburg P. , Barrett B. , Zaal S. , Vonk J. , Morisse F. , Gaese F. , Heinrich M. , Sappok T.
Published: September 2023

Background

Intellectual disability (ID) is often associated with delays in emotional development (ED). The Scale of Emotional Development – Short (SED‐S) was developed to assess the level of ED and to adapt treatment and care accordingly.

Methods

In a sample of 724 adults from five study sites in three countries, a confirmatory factor analysis with a one‐factor model was conducted on the entire dataset as well as in different subgroups. Furthermore, internal consistency was investigated using Cronbach's alpha.

Results

The confirmatory factor analysis indicated that a single‐factor model fits the SED‐S data well. The subgroup analyses revealed good model fit, regardless of the severity of ID and irrespective of sex or the presence of autism spectrum disorder or psychiatric disorders. Internal consistency was excellent for the entire sample (Cronbach's alpha = 0.93) and various subgroups (0.869–0.938).

Conclusion

The results of this study suggest that the SED‐S is psychometrically sound and can be used to assess the level of ED in adults with ID.
Establishing a veterinary anatomy core syllabus through a modified Delphi process
Authors: Gummery Erica , Singh Miren , Channon Sarah B.
Published: September 2023

Anatomy forms a key component of veterinary curricula, but, in the context of an evolving profession, curricula are adapting and changing accordingly. There is a lack of guidance for educators regarding the levels of anatomical knowledge required for a graduate to be considered safe or competent. A formal review of veterinary anatomy learning outcomes (LOs) is therefore timely to support curriculum development in this rapidly evolving field. This study aimed to create a set of LOs which reflect the recommended core requirements for a new graduate veterinarian. A consensus approach using a modified Delphi method was used. The Delphi panel consisted of 23 experienced and active veterinary anatomy educators from veterinary schools within the UK and Ireland. The process had four stages: (1) Research team review, pre‐screening and modification of a list of existing LOs (adapted from the Core Regional Anatomy Syllabus) which then formed the initial set of outcomes sent for review; (2) Delphi Round 1; (3) Delphi Round 2; (4) Post‐Delphi final screening and review. Qualitative data outlining the rationale for modification and rejection of LOs were analysed via content analysis. 167 LOs were initially presented to the Delphi panel in Round 1. 64 of those were accepted, 79 recommended for modification and 23 rejected. 122 LOs were presented to the Delphi panel in Round 2. Of these, 86 outcomes were accepted, 10 modified and 26 rejected. 160 LOs were ultimately accepted and form the Veterinary Anatomy Core Syllabus. Key themes arising from analysis include the removal of unnecessary detail and increased focus on the relevance of competencies required of a new veterinary graduate. The syllabus presented may be used by curriculum planners, teachers and students within veterinary education worldwide.