bluuebunny/crossref_metadata_2025 huggingface dataset:
Low rate of pre-exposure prophylaxis and post-exposure prophylaxis uptake and high prevalence of transmitted drug resistance among newly diagnosed primary HIV infections in Shenzhen, China: a real-world retrospective study
Authors: Peng Qiaoli , Liu Xiaoning , Tang Xian , Zhang Qiuyue , Zhao Jin , Zheng Chenli , Zhao Fang , Zhou Yang , Zhang Lukun , Sun Liqin , Zhang Haitao , Jia Xinyun , Song Ying , Cao Tingzhi , Wang Siyuan , Rao Man , Chen Zhiwei , Wang Hui , He Yun
Published: January 2023

Background:

Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.

Methods:

This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People's Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.

Results:

Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (interquartile range 24.0–34.0); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. In which, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against PI only.

Conclusions:

Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.
Analysis of Multiple Causes of Death: A Review of Methods and Practices
Authors: Bishop Karen , Balogun Saliu , Eynstone-Hinkins James , Moran Lauren , Martin Melonie , Banks Emily , Rao Chalapati , Joshy Grace
Published: January 2023

Background:

Research and reporting of mortality indicators typically focus on a single underlying cause of death selected from multiple causes recorded on a death certificate. The need to incorporate the multiple causes in mortality statistics—reflecting increasing multimorbidity and complex causation patterns—is recognized internationally. This review aims to identify and appraise relevant analytical methods and practices related to multiple causes.

Methods:

We searched Medline, PubMed, Scopus, and Web of Science from their incept ion to December 2020 without language restrictions, supplemented by consultation with international experts. Eligible articles analyzed multiple causes of death from death certificates. The process identified 4,080 items of which we reviewed 434 full-text articles.

Results:

Most articles we reviewed (76%, n = 332) were published since 2001. The majority of articles examined mortality by “any– mention” of the cause of death (87%, n = 377) and assessed pairwise combinations of causes (57%, n = 245). Since 2001, applications of methods emerged to group deaths based on common cause patterns using, for example, cluster analysis (2%, n = 9), and application of multiple-cause weights to re-evaluate mortality burden (1%, n = 5). We describe multiple-cause methods applied to specific research objectives for approaches emerging recently.

Conclusion:

This review confirms rapidly increasing international interest in the analysis of multiple causes of death and provides the most comprehensive overview, to our knowledge, of methods and practices to date. Available multiple-cause methods are diverse but suit a range of research objectives. With greater availability of data and technology, these could be further developed and applied across a range of settings.
Bicuspid aortic valve associated aortopathy: 2022 guideline update
Authors: Verma Raj , Cohen Gideon , Colbert Jillian , Fedak Paul W.M.
Published: January 2023

Purpose of Review

Bicuspid aortic valve (BAV) disease is observed in 1–2% of the general population. In addition to valve-related complications (such as aortic stenosis and aortic regurgitation), individuals with BAV often develop dilatation of the proximal aorta (aortic root and ascending aorta), a condition termed BAV aortopathy. The development of BAV aortopathy can occur independent of valvular alterations and can lead to aneurysm formation, aortic dissection or aortic rupture. This review aims to update the clinician with an approach to BAV aortopathy decision making in keeping with the 2022 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline recommendations.

Recent Findings

The ACC/AHA 2022 guidelines provide a contemporary and comprehensive approach to the diagnosis and treatment of aortic pathologies. We review the thresholds for replacement of the aortic root and/or ascending aorta along with the strength and level of evidence recommendations. We also review the various Class 2A and 2B recommendations for earlier intervention, which emphasize the importance of experienced surgeons, and multidisciplinary aortic teams (MATs).

BAV aortopathy is a common and heterogenous clinical problem. The decision making around timing of intervention requires a personalized approach that is based on the aortic dimensions, valve function, rate of growth, family history, patient factors, and surgical experience within MATs.
Radiation Exposure during Prostatic Artery Embolization: A Single Institution Review
Authors: Ngov Daniel , Self Stella CW. , Schammel Christine MG. , Devane A. Michael
Published: January 2023

Prostate artery embolization is a minimally invasive treatment for benign prostatic hyperplasia, and imaging is indispensable for the technical success of this procedure; however, imaging is a major source of radiation exposure for patients and healthcare providers. Radiation emission during prostate artery embolization procedures at a single institution was evaluated to determine radiation exposure with the goal to work toward minimizing exposure. All patients at a single institution that underwent outpatient unilateral/bilateral prostate artery embolization between 4 January 2019 and 16 November 2021 were retrospectively evaluated; data collected included body mass index, prostate volume, and indications for prostate artery embolization. Technical parameters recorded were air kerma, procedure time, fluoroscopy time, number of acquisitions, and intra-procedural imaging modalities. Fisher’s t-test, ANOVA, and chi-square analyses were used as appropriate for statistical analysis (P < 0.05). Overall, 56 patients were included in the study. Body mass index (obesity; P = 0.0017) was a significant predictor of increased air kerma; prostate size and bilateral vs. unilateral prostate artery embolization were not significantly associated with increased air kerma despite the number of acquisitions being significantly different between bilateral and unilateral embolization (P = 0.0064). When evaluating radiation exposure during prostate artery embolization, increased body mass index significantly predicted increased air kerma. Contrary to the literature, the extent of embolization (bilateral vs. unilateral) was not associated with increased air kerma regardless of higher acquisitions and procedure time associated with bilateral prostate artery embolization. Increased radiation protection efforts should be considered for patients with higher body mass index to protect patients and practitioners.

Health Phys. 124(0):000-000; 2023
Mid- to long-term outcomes of initial transjugular intrahepatic portosystemic shunt versus anticoagulation for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome
Authors: Huang Qianxin , Zhang Qingqiao , Xu Hao , Zu Maoheng , Xiao Jinchang , Shen Bin
Published: January 2023

Background

Anticoagulation therapy (AT) is often used as the initial treatment for pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). However, transjugular intrahepatic portosystemic shunt (TIPS) is an alternative treatment. This study aimed to determine the mid- to long-term outcomes of TIPS versus AT as the initial treatment for PA-induced HSOS.

Methods

We retrospectively analyzed the clinical data of 61 patients with PA-induced HSOS that were collected between November 2015 and July 2021. The patients were allocated to the TIPS group (n = 20) or the AT group (n = 41). These two groups were divided into subgroups according to the severity grading. The clinical data of the patients in both groups were analyzed. Cumulative survival rates were calculated and compared between the two groups and among the subgroups.

Results

The clinical symptoms and signs improved or stabilized in 100% of the patients following TIPS and in 85% of the patients following AT at discharge (P = 0.166). The mortality rate was 0.0% in the TIPS group and 34.1% in the AT group (P = 0.005). The patients were followed up for 2–69 months (mean, 26.3 ± 20.5 months). In the mild- and moderate-grade subgroups, there was no difference in the cumulative survival rate between the TIPS and AT groups (P = 0.589 and P = 0.364, respectively). In the severe and very severe-grade subgroups, the cumulative survival rate was higher in the TIPS group than in the AT group (P = 0.018 and P = 0.025, respectively).

Conclusion

AT is a suitable initial treatment for mild or moderate PA-induced HSOS, whereas TIPS should be considered the appropriate initial treatment for severe or very severe PA-induced HSOS.
Changes in Medical Charges Following Intensive Multidisciplinary Intervention for Pediatric Gastrostomy Tube Dependence
Authors: Dempster Robert , Huston Parker , Castillo Anthony , Sharp William G.
Published: January 2023

Objective:

Intensive multidisciplinary intervention (IMI) is the most evidence-based approach to treat pediatric feeding disorders. The goal of this exploratory study was to assess changes in health care charges for patients with gastrostomy tube dependence following participation in IMI compared to a waitlist control.

Methods:

Medical charges were assessed for 9 families who participated in IMI compared to 6 control families on a multi-year waitlist for IMI. The IMI and control groups were compared on raw charges submitted as well as individual year-over-year changes in medical charges.

Results:

The IMI group decreased health care charges by 71% on average in the year following IMI compared to the control group increasing charges by 22% over the same period.

Conclusions:

IMI also holds potential cost-savings in the year following treatment compared to children who do not receive treatment and adds to previous research focusing on long-term cost effectiveness of IMI.
Community-acquired skin and soft-tissue infections in people who inject drugs
Authors: Allaw Fatima , Zakhour Johnny , Kanj Souha S.
Published: January 2023

Purpose of review

The aim of this review is to discuss the latest evidence of the epidemiology, microbiology, risk factors, diagnosis and management of community-acquired skin and soft tissue infections (SSTIs) in people who inject drug (PWID).

Recent findings

SSTIs are common complications in PWID and a major cause of morbidity and mortality. Infections can range from uncomplicated cellulitis, to abscesses, deep tissue necrosis and necrotizing fasciitis. They are predominantly caused by Gram-positive pathogens in particular Staphylococcus aureus and Streptococcus species; however, toxin-producing organisms such as Clostridium botulism or Clostridium tetani should be considered. The pathogenesis of SSTI in the setting of intravenous drug use (IDU) is different from non-IDU related SSTI, and management often requires surgical interventions in addition to adjunctive antibiotics. Harm reduction strategies and education about safe practices should be implemented to prevent morbidity and mortality as well as healthcare burden of SSTI in PWID.

Prompt diagnosis and proper medical and surgical management of SSTI will improve outcomes in PWID.
In situ wet pharmaceutical granulation captured using synchrotron radiation based dynamic micro-CT
Authors: Ding Xiao Fan , Zeinali Danalou Sima , Zhang Lifeng , Zhu Ning
Published: January 2023

Synchrotron radiation based dynamic micro-computed tomography (micro-CT) is a powerful technique available at synchrotron light sources for investigating evolving microstructures. Wet granulation is the most widely used method of producing pharmaceutical granules, precursors to products like capsules and tablets. Granule microstructures are known to influence product performance, so this is an area for potential application of dynamic CT. Here, lactose monohydrate (LMH) was used as a representative powder to demonstrate dynamic CT capabilities. Wet granulation of LMH has been observed to occur on the order of several seconds, which is too fast for lab-based CT scanners to capture the changing internal structures. The superior X-ray photon flux from synchrotron light sources makes sub-second data acquisition possible and well suited for analysis of the wet-granulation process. Moreover, synchrotron radiation based imaging is non-destructive, does not require altering the sample in any way, and can enhance image contrast with phase-retrieval algorithms. Dynamic CT can bring insights to wet granulation, an area of research previously only studied via 2D and/or ex situ techniques. Through efficient data-processing strategies, dynamic CT can provide quantitative analysis of how the internal microstructure of an LMH granule evolves during the earliest moments of wet granulation. Here, the results revealed granule consolidation, the evolving porosity, and the influence of aggregates on granule porosity.
Climate change disclosure and sustainable development goals (SDGs) of the 2030 agenda: the moderating role of corporate governance
Authors: Toukabri Mohamed , Mohamed Youssef Mohamed Ahmed
Published: January 2023

Purpose

This study is justified by the economic importance of information on greenhouse gases, as well as the interest in the question of governance structure after the adoption of the objectives of the 2030 Agenda. The problem is also explained by the lack of research that has investigated the relationship between the best governance structure that contributes to achieving sustainability goals, including climate actions (SDG13) and clean energy adoption (SDG7) as part of the 2030 Agenda.

Design/methodology/approach

The level of disclosure is measured on the basis of the carbon disclosure score calculated by the carbon disclosure project (CDP). The study sample consists of 387 US companies that voluntarily participated in the CDP survey from 2011 to 2018. The authors use panel data analysis based on multiple regression models.

Findings

The results confirm the influential role of board size, director independence, the presence of women on the board and the presence of an environmental committee on carbon disclosure. In terms of carbon disclosure, the results suggest that a better governance structure is likely to reduce carbon emissions and improve carbon performance practices. Similarly, the analyses show a different representation of the role of corporate governance in high-carbon sectors compared to low-carbon sectors.

Research limitations/implications

This study has some limitations. First, the sample is only interested in US companies that responded to the CDP questionnaire during the period 2011–2018. Thus, the results cannot be generalized to countries with different governance structures. Second, the data from this study on carbon disclosure, specifically focuses on CDP reporting to determine the carbon disclosure score. In this sense, the findings on information disclosed do not necessarily address disclosures through other media, such as a company’s website or a press release.

Originality/value

Sustainability and commitment to the sustainable development goals (SDGs) are more likely to exist in companies that have good governance and, in particular, a better board. The research is inspired by the SDGs. The study aims to examine the relationship between carbon disclosure and corporate governance in the context of SDGs. Indeed, this research work contributes to achieving sustainability goals, including climate actions (SDG13) and clean energy adoption (SDG7).
Literacy and mental health across the globe: a systematic review
Authors: Hunn Lucy , Teague Bonnie , Fisher Paul
Published: January 2023

Purpose

The purpose of this systematic review is to assess if there is a relationship between literacy abilities and mental health outcomes as reported in global literature. Fourteen percent of the global population has little or no literacy. Literacy skills impact on daily functioning and have been shown to impact on social outcomes. Whilst there has been research examining the potential association between literacy and mental health outcomes in specific populations, there has been no systematic review of this literature to date.

Design/methodology/approach

A systematic review was carried out using Embase, PsycINFO and PubMed to identify relevant papers that measured both literacy and mental health. Data relating to the association between literacy and mental health were extracted. The papers included were assessed for quality using a bespoke quality rating tool. A narrative synthesis describes the findings.

Findings

Nineteen studies from across nine countries were included in the analysis. Seventeen studies showed a significant association between literacy and mental health, those with lower literacy had greater mental health difficulties. Some papers reported factors that interacted with this association, such as age, gender, poverty and years of education.

Originality/value

To the best of the authors’ knowledge, this is the first systematic review to look at the global picture of literacy and mental health. It suggests there is a relationship between literacy abilities and mental health outcomes, highlighting the importance of healthcare professionals and services including identification of literacy needs within routine mental health practice.
Environmental drivers of body size in North American bats
Authors: Alston Jesse M. , Keinath Douglas A. , Willis Craig K. R. , Lausen Cori L. , O'Keefe Joy M. , Tyburec Janet D. , Broders Hugh G. , Moosman Paul R. , Carter Timothy C. , Chambers Carol L. , Gillam Erin H. , Geluso Keith , Weller Theodore J. , Burles Douglas W. , Fletcher Quinn E. , Norquay Kaleigh J. O. , Goheen Jacob R.
Published: January 2023

Bergmann's rule—which posits that larger animals live in colder areas—is thought to influence variation in body size within species across space and time, but evidence for this claim is mixed.

We used Bayesian hierarchical models to test four competing hypotheses for spatiotemporal variation in body size within 20 bat species across North America: (1) the heat conservation hypothesis, which posits that increased body size facilitates body heat conservation (and which is the traditional explanation for the mechanism underlying Bergmann's rule); (2) the heat mortality hypothesis, which posits that increased body size increases susceptibility to acute heat stress; (3) the resource availability hypothesis, which posits that increased body size is enabled in areas with more abundant food; and (4) the starvation resistance hypothesis, which posits that increased body size reduces susceptibility to starvation during acute food shortages.

Spatial variation in body mass was most consistently (and negatively) correlated with mean annual temperature, supporting the heat conservation hypothesis. Across time, variation in body mass was most consistently (and positively) correlated with net primary productivity, supporting the resource availability hypothesis.

Climate change could influence body size in animals through both changes in mean annual temperature and resource availability. Rapid reductions in body size associated with increasing temperatures have occurred in short‐lived, fecund species, but such reductions will be obscured by changes in resource availability in longer‐lived, less fecund species.

Read the free Plain Language Summary for this article on the Journal blog.
Advances in immunoassay‐based strategies for mycotoxin detection in food: From single‐mode immunosensors to dual‐mode immunosensors
Authors: Chen Mengting , Qileng Aori , Liang Hongzhi , Lei Hongtao , Liu Weipeng , Liu Yingju
Published: January 2023

Mycotoxin contamination in foods and other goods has become a broad issue owing to serious toxicity, tremendous threat to public safety, and terrible loss of resources. Herein, it is necessary to develop simple, sensitive, inexpensive, and rapid platforms for the detection of mycotoxins. Currently, the limitation of instrumental and chemical methods cannot be massively applied in practice. Immunoassays are considered one of the best candidates for toxin detection due to their simplicity, rapidness, and cost‐effectiveness. Especially, the field of dual‐mode immunosensors and corresponding assays is rapidly developing as an advanced and intersected technology. So, this review summarized the types and detection principles of single‐mode immunosensors including optical and electrical immunosensors in recent years, then focused on developing dual‐mode immunosensors including integrated immunosensors and combined immunosensors to detect mycotoxins, as well as the combination of dual‐mode immunosensors with a portable device for point‐of‐care test. The remaining challenges were discussed with the aim of stimulating future development of dual‐mode immunosensors to accelerate the transformation of scientific laboratory technologies into easy‐to‐operate and rapid detection platforms.
Immunoadsorption to treat patients with severe post‐COVID syndrome
Authors: Giszas Benjamin , Reuken Philipp A. , Katzer Katrin , Kiehntopf Michael , Schmerler Diana , Rummler Silke , Stallmach Andreas , Klink Anne
Published: January 2023

Introduction

Following SARS‐CoV‐2‐infection up to 21% of patients will develop post‐COVID‐syndrome. Autoantibodies (AAbs) targeting neuronal‐ß‐adrenergic and muscarinic receptors may provide crucial contributions to the pathophysiology of this condition. Immunoadsorption (IA) has been identified as an effective means of removing AAbs and has resulted in clinical improvements of other autoantibody‐associated diseases.

Methods

We determined AAb‐levels (anti‐ß1/ß2 and anti‐M3/M4 receptor) in 178 patients diagnosed with post‐COVID‐syndrome and described the clinical courses of two patients with elevated AAb‐levels that underwent IA‐treatment.

Results

AAbs were detected in 57% (101/178) of patients diagnosed with post‐COVID‐syndrome. Substantial reductions in AAb‐levels and clinical remission were achieved in one of two patients who was treated with IA. However, this patient relapsed within 6 weeks with a concomitant increase in AAb‐levels.

Conclusion

Collectively, AAbs may play a pathophysiologic role in post‐COVID and their removal provide transient benefits in some patients. However, these findings should be further investigated in randomized‐controlled‐trials.
Respiratory insufficiency as a presenting symptom of congenital myasthenic syndromes
Authors: van den Udenhout Fleur , Merkus Peter , Verhaagen‐van den Akker Sandra , Schouten Meyke , Erasmus Corrie , Braakman Hilde
Published: January 2023

Aim

Respiratory insufficiency can be a presenting symptom of congenital myasthenic syndromes (CMS) but is rarely recognised as such. In this study, we aim to raise awareness of CMS to paediatricians.

Methods

We performed a retrospective case study of infants and preschool children treated in the past 5 years in Amalia Children's Hospital, Radboud University Medical Center in Nijmegen, the Netherlands for respiratory insufficiency as presenting symptom of CMS.

Results

Five children aged 2 weeks to 5 years experienced severe to life‐threatening episodes of respiratory insufficiency, especially during viral infections, due to respiratory muscle weakness. During infections, they often also had progression of their otherwise mild ocular, facial, and limb muscle weakness. They were eventually diagnosed with genetically proven CMS. In these five children, treatment with pyridostigmine, an acetylcholinesterase inhibitor, resulted in clinical improvement.

Conclusion

CMS should be considered in every patient with unexplained recurrent respiratory insufficiency, or with an unusually severe course of a normally mild respiratory infection, especially in combination with mild muscle weakness outside periods of illness. Early diagnosis of CMS is crucial for early treatment, which may help avoiding sudden infant death, severe respiratory insufficiency and further deterioration of the muscle strength.
Accurate intraoperative real‐time blood flow assessment of the remnant stomach during robot‐assisted distal pancreatectomy with celiac axis resection using indocyanine green fluorescence imaging and da Vinci Firefly technology
Authors: Saito Kenta , Morimoto Mamoru , Denda Yuki , Nonoyama Keisuke , Murase Hiromichi , Kato Tomokatsu , Hayashi Yuichi , Imafuji Hiroyuki , Ogawa Ryo , Takahashi Hiroki , Matsuo Yoichi , Takiguchi Shuji
Published: January 2023

Introduction

Ischemic gastropathy is one of the unique postoperative complications associated with distal pancreatectomy with celiac axis resection for locally advanced pancreatic cancer. Therefore, it is essential to evaluate blood flow to the stomach following a resection; however, no intraoperative procedures have been established to assess this issue. Herein we describe two cases in which intraoperative evaluation of real‐time blood flow in the residual stomach was performed using indocyanine green fluorescence and da Vinci Firefly technology during a robot‐assisted distal pancreatectomy with celiac axis resection.

Methods

Robot‐assisted distal pancreatectomy with celiac axis resection was performed using a da Vinci Xi surgical system on two patients with locally advanced pancreatic cancer and suspected invasion of the celiac artery. Indocyanine green (ICG) (0.5 mg/kg) was injected intravenously after resection to evaluate real‐time blood flow of the stomach using the da Vinci Firefly system. Blood flow of the stomach was evaluated 60 seconds after the intravenous injection of ICG.

Results

All cases were confirmed that there was sufficient blood flow in the residual stomach. Therefore, reconstruction of the left gastric artery was not performed, and the surgery was completed with preservation of the stomach. Good postoperative outcomes were achieved and there was no evidence of ischemic gastropathy or delayed gastric emptying in both cases.

Conclusion

This method is very useful in determining whether or not to perform reconstruction of the left gastric artery and/or additional resection of the remnant stomach during a robot‐assisted distal pancreatectomy with celiac axis resection.
Evaluation of the inhibitory effects of itraconazole on letermovir
Authors: McCrea Jacqueline B. , Menzel Karsten , Fancourt Craig , Witter Rose , Zhao Tian , Robbins Jonathan A. , Stoch S. Aubrey , Iwamoto Marian
Published: January 2023

Aims

Letermovir, a cytomegalovirus (CMV) DNA terminase complex inhibitor, is a substrate of ABCB1 (P‐glycoprotein; P‐gp), organic anion transporting polypeptide (OATP)1B1/3, UDP‐glucuronosyltransferase (UGT)1A1, UGT1A3 and possibly ABCG2 (breast cancer resistance protein; BCRP). A study was conducted to evaluate the effects of itraconazole, a prototypic ABCB1/ABCG2 inhibitor, on letermovir pharmacokinetics (PK) and the effects of letermovir on itraconazole PK.

Methods

In an open‐label, fixed‐sequence study in 14 healthy participants, 200 mg oral itraconazole was administered once daily for 4 days. Following a 10‐day washout, 480 mg oral letermovir was administered once daily for 14 days (Days 1–14) and then coadministered with 200 mg itraconazole once daily for 4 days (Days 15–18). Intensive PK sampling was performed for letermovir and itraconazole. PK and safety were evaluated.

Results

Letermovir geometric mean ratio (GMR; 90% confidence interval [CI]) for area under the concentration–time curve from time 0 to 24 h (AUC0–24) was 1.33 (1.17, 1.51) and for maximum concentration (Cmax) was 1.21 (1.05, 1.39) following administration with/without itraconazole. Itraconazole GMR (90% CI) for AUC0–24 was 0.76 (0.71, 0.81) and for Cmax was 0.84 (0.76, 0.92) following administration with/without letermovir. Coadministration of letermovir with itraconazole was generally well tolerated.

Conclusions

The increase in letermovir exposure with coadministration of itraconazole is likely predominantly due to inhibition of intestinal ABCB1 and potentially ABCG2 transport. The mechanism for the decrease in itraconazole exposure is unknown. The modest changes in letermovir and itraconazole PK are not considered clinically meaningful.
Studying the imaging features and infarction mechanism of vertebrobasilar dolichoectasia with high‐resolution magnetic resonance imaging
Authors: Zheng Tao , Tang Wenxiong , Shan Yi , Guo Runcai , Gao Yang , Tian Chaohui , Liu Lei , Sun Lili , Liu Wei , Zhou Zhi , Jin Yi , Duan Shaojie , Han Bingyu , Fan Yangyi , Zhu Xianjin , Liu Zunjing
Published: January 2023

The mechanisms underlying ischemic infarction in patients with vertebrobasilar dolichoectasia (VBD) remain unclear. In this study, we retrospectively analyzed the imaging characteristics of high‐resolution magnetic resonance imaging (HR‐MRI) in patients with VBD to explore the possible mechanisms of ischemic stroke (IS) in patients with VBD. Patients with VBD were recruited from the HR‐MRI database between July 2017 and June 2021. HR‐MRI was used to evaluate the diameter, bifurcation height, laterality, arterial dissection, and atherosclerotic plaques of the basilar artery (BA). Transcranial Doppler was used to measure the vertebrobasilar mean velocity (Vm), peak systolic velocity (Vs), end‐diastolic velocity (Vd), and pulsatile index. Twenty‐six patients with VBD were enrolled, of which 15 had IS and 11 did not. The incidence of classical vascular risk factors, including age, sex, hypertension, diabetes, and hypercholesterolemia, did not differ significantly between the two groups. The BA diameters of the stroke group were significantly higher than that of the nonstroke group (6.57 ± 1.00 mm vs. 5.06 ± 0.50 mm, p = 0.000). The height of the BA bifurcation in the stroke and nonstroke groups was statistically significant (p = 0.002). Compared with the nonstroke group, the Vm, Vs, and Vd of the BA in the stroke group were lower, but the difference was not significant. In the 16 patients with atherosclerotic stenosis, 30 atherosclerotic plaques were found in the BA, 18 (60%) in the greater curvature, and 12 (40%) in the lesser curvature. In addition, one artery dissection (on the lesser curvature) and two dissecting aneurysms (on the greater curvature) were found in the BA of three patients, respectively. The BA diameter and bifurcation height are factors related to IS in patients with VBD. The mechanism of stroke in patients with VBD may involve abnormal hemodynamics, artery dissection, and atherosclerosis. HR‐MRI is a useful method for evaluating the risk and underlying mechanism of stroke in patients with VBD.
GNB1 promotes hepatocellular carcinoma progression by targeting BAG2 to activate P38/MAPK signaling
Authors: Zhang Xin , Dong Keshuai , Zhang Jiacheng , Kuang Tianrui , Luo Yiyun , Yu Jia , Yu Jinming , Wang Weixing
Published: January 2023

G‐proteins are intracellular partners of G‐protein‐coupled receptors. As a member of the G‐protein family, GNB1 has been shown to play a pro‐cancer role in lung cancer and breast cancer. However, the biological function and detailed mechanisms of GNB1 in hepatocellular carcinoma progression are unclear. In this study, we investigated the effects of GNB1 and its possible mechanism of action in hepatocellular carcinoma (HCC). The clinical significance of GNB1 was evaluated in a large cohort of HCC patients, showing that GNB1 was overexpressed in HCC compared to adjacent normal liver tissues, and increased GNB1 expression was associated with poor prognosis. We also demonstrated that GNB1 enhances cell proliferation, colony formation, and cell migration and invasion in vitro and promotes the epithelial‐to‐mesenchymal transition process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of GNB1 in tumorigenicity in nude mice. Activation of P38 signaling was found in the GNB1 overexpressed HCC cells. Further intervention of P38 confirmed it as an important signaling pathway for the oncogenic role of GNB1 in HCC. Moreover, co‐immunoprecipitation followed by liquid chromatograph‐mass spectrometry identified that GNB1 exerted oncogenic functions via the interaction of BAG2 and activated P38 signaling pathway. Together, our results reveal that GNB1 plays a pivotal oncogenic role in HCC by promoting the P38 pathway via cooperating with BAG2. GNB1 may serve as a prognostic biomarker for patients with HCC.
Performance of an artificial intelligence automated system for diabetic eye screening in a large English population
Authors: Meredith Sarah , van Grinsven Mark , Engelberts Jonne , Clarke Dominic , Prior Vicki , Vodrey Jo , Hammond Alison , Muhammed Raja , Kirby Philip
Published: January 2023

Aims

A diabetic eye screening programme has huge value in reducing avoidable sight loss by identifying diabetic retinopathy at a stage when it can be treated. Artificial intelligence automated systems can be used for diabetic eye screening but are not employed in the national English Diabetic Eye Screening Programme. The aim was to report the performance of a commercially available deep‐learning artificial intelligence software in a large English population.

Methods

9817 anonymised image sets from 10,000 consecutive diabetic eye screening episodes were presented to an artificial intelligence software. The sensitivity and specificity of the artificial intelligence system for detecting diabetic retinopathy were determined using the diabetic eye screening programme manual grade according to national protocols as the reference standard.

Results

For no diabetic retinopathy versus any diabetic retinopathy, the sensitivity of the artificial intelligence grading system was 69.7% and specificity 92.2%. The performance of the artificial intelligence system was superior for no or mild diabetic retinopathy versus significant or referrable diabetic retinopathy with a sensitivity of 95.4% and specificity of 92.0%. No cases were identified in which the artificial intelligence grade had missed significant diabetic retinopathy.

Conclusion

The performance of a commercially available deep‐learning artificial intelligence system for identifying diabetic retinopathy in an English national Diabetic Eye Screening Programme is presented. Using the pre‐defined settings artificial intelligence performance was highest when identifying diabetic retinopathy which requires an action by the screening programme.
Strategy maps: Generalised giving‐up densities for optimal foraging
Authors: Arehart Emerson , Reimer Jody R. , Adler Frederick R.
Published: January 2023

Finding a common currency for benefits and hazards is a major challenge in optimal foraging theory, often requiring complex computational methods. We present a new analytic approach that builds on the Marginal Value Theorem and giving‐up densities while incorporating the nonlinear effect of predation risk. We map the space of all possible environments into strategy regions, each corresponding to a discrete optimal strategy. This provides a generalised quantitative measure of the trade‐off between foraging rewards and hazards. This extends a classic optimal diet choice rule‐of‐thumb to incorporate the hazard of waiting for better resources to appear. We compare the dynamics of optimal decision‐making for three foraging life‐history strategies: One in which fitness accrues instantly, and two with delays before fitness benefit is accrued. Foragers with delayed‐benefit strategies are more sensitive to predation risk than resource quality, as they stand to lose more fitness from a predation event than instant‐accrual foragers.
Spatial transformer network on skeleton‐based gait recognition
Authors: Zhang Cun , Chen Xing‐Peng , Han Guo‐Qiang , Liu Xiang‐Jie
Published: January 2023

Skeleton‐based gait recognition models suffer from the robustness problem, as the rank‐1 accuracy varies from 90% in normal walking cases to 70% in walking with coats cases. In this work, we propose a state‐of‐the‐art robust skeleton‐based gait recognition model called Gait‐TR, which is based on the combination of spatial transformer frameworks and temporal convolutional networks. Gait‐TR achieves substantial improvements over other skeleton‐based gait models with higher accuracy and better robustness on the well‐known gait dataset CASIA‐B. Particularly in walking with coats cases, Gait‐TR gets a ∼90% accuracy rate. This result is higher than the best result of silhouette‐based models, which usually have higher accuracy than the skeleton‐based gait recognition models. Moreover, our experiment on CASIA‐B shows that the spatial transformer network can extract gait features from the human skeleton better than the widely used graph convolutional network.
Language and symbolic boundaries among transnational elites: A qualitative case study of European Commission officials
Authors: Drewski Daniel
Published: January 2023

Previous research has asked whether European integration leads to the formation of a new kind of ‘transnational class’ or ‘elite’ in and around the European institutions in Brussels. This paper focuses instead on intra‐group distinctions and symbolic boundaries between EU professionals from different countries. Drawing on Bourdieu’s notion of language as a marker of distinction, it argues that language continues to be a resource for symbolic boundary making. Empirically, this paper builds on in‐depth interviews with officials of the European Commission, who are at the heart of an emerging transnational elite of EU professionals. It shows that while Commission officials are multilingual and use multilingualism to construct themselves as a transnational group, intra‐group symbolic boundaries continue to be drawn based on competence in the Commission’s two main working languages, English and French. Overall, this paper points out the overlooked importance of language differences for transnational professionals’ symbolic boundary making.
‘Mind your language’: What people in prison think about the language used to describe them
Authors: Bidwell Lili , Polley Laura
Published: January 2023

This study investigated how people in prison feel about the language used to describe them and how it affected them. Previous research shows that terminology used to describe people in prison affects their self‐identity, namely through its shame‐inducing effects. A thematic analysis of qualitative data gathered through interviews demonstrated that language impacts how an individual in prison engages with the community and how they view themselves. Positive and progressive language in prisons has the potential to remove the shame and stigma attached to the prisoner identity.
Kinetic modeling of four folates in a model solution at different temperatures and pH to mimic their behavior in foods during processing
Authors: Servent Adrien , Cazals Guillaume , Perfetto Carmen , Achir Nawel
Published: January 2023

This study aims to generate new kinetic data on 4 folate forms, namely folic acid (FA), 5‐methyl‐tetrahydrofolate (5MTHF), 10‐formylfolic acid (10FFA) and tetrahydrofolate (THF) in the same conditions: model media at three temperatures (60°C, 80°C, and 100°C) and three pH values (3, 5, and 7). For the four forms, degradation could be described using a first‐order model. At 100°C and pH 3, rates were 2.8 × 10−2, 1.6 × 10−2, 1.8 × 10−3, and 4 × 10−5 min−1 for 5MTHF, THF, 10FFA and FA respectively. Therefore, the reactivity could be modulated by a factor of 2, 10, and up to 200‐fold for folic acid. pH increase had a positive effect on retention for THF and FA and has the lowest impact on 5MTHF degradation. Product formation from 5MTHF and 10 FFA were studied by multiresponse modeling. Both vitamers generated intermediary products that accumulated differently as a function of pH. These results give comprehension and kinetic insights into folate degradation during food processing from the formulation (pH lever) to the process (temperature lever).

Practical Applications

This article brings new insights into vitamins B9 degradation during cooking. Folate is a group of vitamins, sharing a similar molecular structure while having different bioactivity. The lack of folate in diet can lead to severe health disorder. Their human metabolization and thermic degradation can be influenced by different factors, including their own structure. Therefore, it is of high importance to understand how each form is degraded and to determine the best formulation and process conditions to preserve them. Our work, in model mediums, allowed to identify four folate forms reactivity and degradation (including degradation pathway) in order to give more guidance, and offers an operational tool for manufacturer to determine the potential retention of folates as a function of pH, temperature and vitamer composition.
ZO‐1 expression in normal human macula densa: Immunohistochemical and immunofluorescence investigations
Authors: Tossetta Giovanni , Fantone Sonia , Senzacqua Martina , Galosi Andrea Benedetto , Marzioni Daniela , Morroni Manrico
Published: January 2023

The macula densa (MD) is an anatomical structure having a plaque shape, placed in the distal end of thick ascending limb of each nephron and belonging to juxtaglomerular apparatus (JGA). The aim of the present investigation is to investigate the presence of ZO‐1, a specific marker of tight juncions (TJs), in MD cells. Six samples of normal human renal tissue were embedded in paraffin for ZO‐1 expression analysis by immunohistochemical and immunofluorescence techniques. We detected ZO‐1 expression in the apical part of cell membrane in MD cells by immunohistochemistry. In addition, ZO‐1 and nNOS expressions (a specific marker of MD) were colocalized in MD cells providing clear evidence of TJs presence in normal human MD. Since ZO‐1 is responsible for diffusion barrier formation, its presence in the MD supports the existence of a tubulomesangial barrier that ensures a regulated exchange between MD and JGA effectors in renal and glomerular haemodynamic homeostasis.
The efficacy of adding topical 5‐fluorouracil to micro‐needling in the treatment of vitiligo: A randomized controlled trial
Authors: Pazyar Nader , Hatami Mohammad , Yaghoobi Reza , Parvar Seyedeh Yasamin , Radmanesh Mohammad , Hadibarhaghtalab Maryam
Published: January 2023

Background and Aim

Vitiligo is an autoimmune skin disorder characterized by circumscribed depigmented macules and patches caused by the loss of functional melanocytes. Although there is no definitive treatment for vitiligo, several treatment options have been associated with relative satisfactory outcomes. The purpose of this study was to compare the efficacy of micro‐needling in conjunction with topical 5‐fluorouracil (5‐FU) versus topical tacrolimus ointment in treating vitiligo patches.

Patients and Methods

This study included nineteen participants, each of whom received both treatments on two randomly selected vitiligo patches of approximately the same size and location. On one patch, a combination of weekly micro‐needling and topical application of 5‐FU solution was used every other day, while on the other, 0.1% tacrolimus topical ointment was applied twice daily. The G‐score was used to compare treatment outcomes after 3 months.

Results

The median duration of the disease in our population was 7 years. Six patients (32%) in the micro‐needling plus topical 5‐FU treated group showed a moderate to excellent response, indicating a significant improvement between both treatments (p‐value = 0.019). In contrast, all other patches treated with topical tacrolimus showed poor improvement. Lower extremity and trunk responded more to treatment with micro‐needling plus topical 5‐FU than upper extremity and acral areas. Moreover, none of those who have had the disease for more than ten years have responded to treatment. Mild erythema, pinpoint bleeding, and irritation were detected only in the micro‐needling treated group.

Conclusion

The current study showed that using micro‐needling in conjunction with 5‐FU could treat vitiligo patients more efficiently than tacrolimus monotherapy. Despite showing moderate to excellent improvement in patches treated with micro‐needling and 5‐FU, this well‐tolerated office‐based modality still requires additional research.
An umbrella review of the use of platelet‐rich plasma in the treatment of androgenetic alopecia
Authors: Li Caihong , Pan Lingfeng , Yang Liehao , Kong Jiao , Zhang Lianbo
Published: January 2023

Objective

To evaluate the efficacy of platelet‐rich plasma (PRP) in the treatment of androgenetic alopecia, as well as establish an effective treatment protocol and optimal PRP preparation procedure.

Methods

We searched the PubMed, Scopus, Embase, Cochrane, CNKI, and Wanfang databases from inception to October 29, 2021, using PROSPERO's International Prospective Register of Systematic Reviews (registration ID: CRD42022295921).

Results

The original literature search revealed 215 reviews; after duplication removal, 89 papers were eliminated, 95 were eliminated after reading the titles and abstracts, and eventually, 28 articles were included after reading the complete text.

Conclusions

PRP treatment for androgenetic alopecia is effective, and we recommend the following: (1) a PRP volume of at least 0.05 ml/cm2, preferably 0.1 ml/cm2; (2) at least three consecutive treatments at an interval of 1 month; (3) intensive therapy is beneficial and can be provided from 3 to 6 months after continuous treatment; (4) objective indicators such as hair diameter, hair count; (5) long‐term follow‐up.