bluuebunny/crossref_metadata_2025 huggingface dataset:
26. Economic and Monetary Union
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The Area of Freedom, Security, and Justice (AFSJ) is now found in Title V of Part Three of the Treaty on the Functioning of the European Union. The subject matter dealt with by these provisions is important and politically sensitive, as it includes police and judicial cooperation in criminal matters, visas, asylum, immigration, and judicial cooperation in civil matters. This chapter is organized as follows. Section 2 considers the development of the three-pillar structure introduced by the Maastricht Treaty. Section 3 focuses on the rationale for the inclusion of the subject matter that comprises the AFSJ. Section 4 considers the general principles in the Lisbon Treaty that apply to all areas which comprise the AFSJ, including: Treaty objectives, competence, role of the principal EU institutions, judicial role, and an outline of the opt-outs that apply to the UK. The remainder of the chapter looks in more detail at criminal law and procedure. The UK version contains a further section analysing issues concerning the AFSJ and the UK post-Brexit.
27. AFSJ: EU Criminal Law
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The Area of Freedom, Security, and Justice (AFSJ) is now found in Title V of Part Three of the Treaty on the Functioning of the European Union. The subject matter dealt with by these provisions is important and politically sensitive, as it includes police and judicial cooperation in criminal matters, visas, asylum, immigration, and judicial cooperation in civil matters. This chapter is organized as follows. Section 2 considers the development of the three-pillar structure introduced by the Maastricht Treaty. Section 3 focuses on the rationale for the inclusion of the subject matter that comprises the AFSJ. Section 4 considers the general principles in the Lisbon Treaty that apply to all areas which comprise the AFSJ, including: Treaty objectives, competence, role of the principal EU institutions, judicial role, and an outline of the opt-outs that apply to the UK. The remainder of the chapter looks in more detail at criminal law and procedure. The UK version contains a further section analysing issues concerning the AFSJ and the UK post-Brexit.
13. Enforcement Actions Against Member States
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. A crucial component of the Commission’s task is to monitor Member State compliance and to respond to non-compliance. The Treaty on the Functioning of the European Union (TFEU) provides for various enforcement mechanisms involving judicial proceedings against the Member States, which are brought either by the Commission or—much less frequently—by a Member State. Article 258 TFEU establishes the general enforcement procedure, giving the Commission broad power to bring enforcement proceedings against Member States that it considers to be in breach of their obligations under EU law. This chapter discusses the function and operation of the infringement procedure; the relationship between ‘public’ and ‘private’ enforcement mechanisms; the Commission’s discretion; types of breach by Member States of EU law; state defences in enforcement proceedings; and the consequences of an Article 258 ruling. The UK version contains a further section analysing the extent to which Article 258 is relevant to the UK post-Brexit.
22. Free Movement of Workers
Authors: Craig Paul , de Búrca Gráinne
Published: September 2024

All books in this flagship series contain carefully selected substantial extracts from key cases, legislation, and academic debate, providing students with a stand-alone resource. The free movement of workers is of central importance to the EU, in both economic and social terms. This is reflected in the legislation that fleshes out the basic rights contained in Article 45 and in the European Court of Justice’s consistently purposive interpretation of the Treaty Articles and legislation to achieve the EU’s objectives in this area. This chapter considers several central legal issues that arise in the context of the free movement of workers. These include the scope of Article 45, the meaning accorded to ‘worker’, the rights of intermediate categories such as ‘job-seeker’, the kinds of restrictions that states may justifiably impose on workers and their families; and the rights which family members enjoy under EU law. The UK version contains a further section analysing issues concerning free movement of workers between the EU and the UK post-Brexit.
Bradgate's Commercial Law
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

Bradgate's Commercial Law provides comprehensive coverage of the principles of commercial law alongside critical discussion. It offers rigorous in-depth analysis and a modern, contextual approach which draws links to the practice of commercial law. This edition includes new chapters on international trade, foreign investment, and the future trajectory of the subject. There is expanded coverage of territorial matters, the law of the sea, and maritime delimitation, with the aim to reflect advances in the area. Also, chapters have been updated to include detailed explanation of topics such as international organisations, international environmental law, the law of treaties, and legal subjects. All chapters have been revised to incorporate new developments and all major judgments in the area.
9. The contract of sale and the classification of transactions
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter discusses the contract of sale and the classification of transactions. It highlights the importance of understanding the differences between the different types of supply contracts. Different arrangements of ownership and possession of goods may offer the parties a range of advantages and their popularity may vary from time to time according to changes in several factors like commercial practice and economic circumstances. The Consumer Rights Act 2015 (CRA) provides a distinct legislative regime for consumer protection that ranges around sales and other supply contracts. The chapter then details how different transactions are classified, which includes hire purchase, conditional sale, and computer software.
14. The duty to pass a good title
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter considers the duty to pass a good title. It defines the key concepts surrounding property, title, and the right to sell. The courts treat the failure to pass a good title as a fundamental failure on the part of the seller so that the buyer can end the contract and obtain their full purchase price without any reduction for the use of the goods. Meanwhile, section 12 of the Sale of Goods Act 1979 (SGA) cannot be excluded by any contract term. However, the provision does allow the seller to effectively avoid liability for breach of the implied warranties if they can reveal any relevant encumbrance or charge before the contract.
27. Bills of lading and contracts of carriage
Authors: Beheshti Reza , Saintier Séverine , Thomas Sean
Published: September 2024

This chapter focuses on the key concepts of bills of lading and contracts of carriage. It highlights the importance of contracts of carriage since goods sold to an international sale contract need to arrange transportation to particular destinations. Goods are often carried under a waybill contract under which the carrier undertakes to deliver the goods to a named consignee at the port of destination. The chapter considers the bill of lading as a document of title, as evidence of the contract of carriage, and as a receipt before listing alternatives to bills of lading. It also looks into tort claims against third parties and claims against the carrier.
Life Out of the Shadows: the Impacts of Regularization Programs on the Lives of Forced Migrants
Authors: Ibáñez Ana María , Moya Andrés , Ortega María Adelaida , Rozo Sandra V , Urbina Maria José
Published: September 2024

We examine the well-being effects of a regularization program offered to half a million Venezuelan forced migrants in Colombia. We collected data on more than 2000 such migrants and compared the well-being of those who arrived in Colombia before and after the date that defined program eligibility. Since this date was announced ex-post and was unknown to the public, we could credibly evaluate the program’s impact. We find that program beneficiaries experienced large improvements in well-being, including consumption per capita (a gain of 48%), monthly labor income (an increase of 22%), and health status (an increment of 1.2 standard deviations). These positive outcomes largely stemmed from improved access to services, particularly the social protection system, subsidized healthcare system, and financial services. We also find that the fiscal costs incurred by the Colombian government for a regularized migrant household are lower than those for an irregular migrant household.
Burden and Risk Factors of Cervical Spine Conditions in Military Aircrew From 1997 to 2015: A Retrospective Cohort Study
Authors: Lang Richard W , Porensky Paul , Fraser John J
Published: September 2024

Introduction

Military aviators may have increased risk of cervical spine injuries because of exposure to supraphysiologic forces and vibration during dynamic flight. Aviator medical attrition impairs mission readiness, decreases operational capabilities, increases overall DoDcosts, and decreases retention of seasoned aviators. This study evaluated incidence and risk factors for cervical spine conditions in U.S. military aviators from 1997 to 2015.

Materials and Methods

The Defense Medical Epidemiological Database was queried for aviators with a diagnosis of cervical spine conditions. Pertinent ICD-9 codes for cervical spine pathology were ascertained from U.S. Army, Air Force, and Naval Air Forces aeromedical references. Negative binomial regressions assessed sex, age, service, aircraft, and year on incidence of conditions. Rates were compared to non-aviator controls. The study was approved by the Institutional Review Board at the Naval Health Research Center (NHRC.2020.0205-NHSR).

Results

Incidence rates were 9.78 to 12.57/1,000 person-years for neck pain, 2.04 to 3.89/1,000 person-years for degenerative conditions without neurological involvement, and 0.94 to 1.36/1,000 person-years for degenerative conditions with neurological involvement. Aviation occupation (relative risk [RR] 1.41–2.05), female sex (RR 3.32–7.89), age over 40 (RR 2.39–4.62), and service in the Army or Marine Corps (RR 1.62–2.14) were risk factors.

Conclusions

Military aviators had a statistically significant increase in risk of neck pain and medically disqualifying degenerative cervical spine conditions compared to non-aviator controls. Rates of neck pain increased in all aviators over the study epoch. Possible explanations could be related to the operational demands and the increased use of forward helmet-mounted display systems during the study period, a supposition that requires further investigation. There was no significant difference in rates of neck pain or degenerative cervical conditions between aircraft platforms (fighter/bomber, other fixed wing, and rotary wing). Female sex, age over 40 years, and Army/Marine Corps service were the greatest risk factors for neck pain and degenerative cervical spine conditions. Targeted prevention programs and expanded treatment modalities are necessary to reduce aviator attrition and Department of Defense cost burden.
Unveiling the interfacial liquid in electrochemical reactions
Authors: Nicolas Joseph , Baidoun Rani , Kim Dohyung
Published: September 2024

Adapting novel experimental techniques to address key knowledge gaps about the structure and properties of the interfacial liquid (IL) will enhance our understanding of its influence on electrochemical reactions, particularly in mediating species transport, charge transfer, and intermediate stability.
An Opt-Out Emergency Department Screening Intervention Leads to Major Increases in Diagnosis of Syphilis
Authors: Stanford Kimberly A , Mason Joseph , Friedman Eleanor , Hazra Aniruddha , Augustine Erin , Schneider John
Published: September 2024

Background

With rising rates of syphilis in the United States, novel strategies are needed to improve early diagnosis, particularly among priority populations such as pregnant people. As the primary source of healthcare for many communities with limited access to care, the emergency department (ED) visit represents a crucial opportunity for syphilis detection and congenital syphilis prevention.

Methods

This pre–post design study examined all ED encounters for 2-year periods before and after implementation of an opt-out ED syphilis screening intervention in May 2019 at a large, urban, academic ED. Data on laboratory testing, syphilis status, and demographics were extracted from the medical record. Descriptive statistics and logistic regression were used to examine trends in syphilis screening and diagnosis.

Results

Syphilis screening increased from 5209 (3.6%) to 37 289 (24.4%) encounters. Presumed active syphilis infection (PAI) increased 288%, from 161 patients (3.1% of those screened) to 624 (1.7%). The proportion of female PAI increased from 25.6% to 42.5%, despite no change in proportion of females screened. Post-intervention, 23.6% of PAI were tested for a urogenital sexually transmitted infection (STI) in the ED and 9.0% presented with symptoms of an STI by diagnosis code. Among pregnant people, screening increased from 5.9% to 49.9% of encounters, and syphilis diagnosis increased 750%, from 2 cases to 15.

Conclusions

Opt-out ED syphilis screening led to a dramatic increase in screening and diagnosis, especially among pregnant individuals, a priority population for congenital syphilis prevention. Most individuals with syphilis did not have STI symptoms. Opt-out screening will be an important strategy in the effort to address the syphilis epidemic.
Contrasting dynamics of two incursions of low-pathogenicity avian influenza virus into Australia
Authors: Wille Michelle , Broz Ivano , Cherrington Tanya , Crawley Allison , Farrugia Blaine , Ford Mark , Frost Melinda , Grimsey Joanne , Kirkland Peter D , Latimore Shaylie , Lynch Stacey E , Martin Sue , Matereke Cornelius , Mee Peter T , Neave Matthew J , O’Dea Mark , Read Andrew J , O’Riley Kim , Stevens Vittoria , Thayaparan Sivapiragasam , Zufan Sara , Ban de Gouvea Pedroso Silvia , Grillo Victoria , Breed Andrew C , Barr Ian G , Holmes Edward C , Klaassen Marcel , Wong Frank Y.K
Published: September 2024

The current panzootic of high pathogenicity avian influenza virus H5N1 demonstrates how viral incursions can have major ramifications for wildlife and domestic animals. Herein, we describe the recent incursion into Australia of two low pathogenicity avian influenza virus subtypes, H4 and H10, that exhibited contrasting evolutionary dynamics. Viruses detected from national surveillance and disease investigations between 2020 and 2022 revealed 27 genomes, 24 of which have at least one segment more closely related to Eurasian or North American avian influenza lineages than those already circulating in Australia. Phylogenetic analysis revealed that H4 viruses circulating in shorebirds represent a recent incursion from Asia that is distinct from those circulating concurrently in Australian waterfowl. Analysis of the internal segments further demonstrates exclusive, persistent circulation in shorebirds. This contrasts with H10, where a novel lineage has emerged in wild waterfowl, poultry, and captive birds across Australia and has likely replaced previously circulating H10 lineages through competitive exclusion. Elucidating different dynamics for avian influenza incursions supports effective disease risk identification and communication that better informs disease preparedness and response.
Auditory Prognosis of Patients With Sudden Sensorineural Hearing Loss in Relation to the Presence of Acute Vestibular Syndrome: A Systematic Literature Review and Meta-Analysis
Authors: González-García Miriam , Prieto-Sánchez-de-Puerta Lucía , Domínguez-Durán Emilio , Sánchez-Gómez Serafín
Published: September 2024

Objectives:

Hearing recovery following idiopathic sudden sensorineural hearing loss (ISSNHL) is influenced by various prognostic factors, and the presence of acute vestibular syndrome (AVS) may adversely impact auditory outcomes. Evaluating vestibular function in SSNHL patients could offer insights into predicting hearing recovery. This systematic review aims to assess whether the presence of AVS exacerbates the audiological prognosis of ISSNHL.

Design:

A comprehensive systematic review was conducted using databases such as PubMed, Cochrane Library, EMBASE, and Scopus, encompassing articles published in the last decade. Included were retrospective and prospective case-control and cohort studies, as well as randomized clinical trials. Meta-analysis was performed based on the findings from these studies.

Results:

Among 386 articles identified, six addressed the systematic review’s question, all being retrospective studies. These articles collectively involved 393 patients for the meta-analysis. Vestibular function assessment methods varied widely, posing challenges for direct comparisons. The likelihood of unfavorable hearing outcomes was 2.29 times higher in patients with associated AVS. Hearing recovery was 3.22 times more likely to be worse in patients with altered cervical vestibular evoked myogenic potentials-air-conducted sound. Abnormal caloric test results showed no significant association with worse hearing prognosis, although patients with unaltered caloric tests demonstrated a significantly greater improvement in pure-tone audiometry.

Conclusions:

Hearing recovery from ISSNHL appears to be diminished in patients with associated AVS and abnormal vestibular test results.
Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19
Authors: Karakike Eleni , Metallidis Simeon , Poulakou Garyfallia , Kosmidou Maria , Gatselis Nikolaos K. , Petrakis Vasileios , Rovina Nikoletta , Gkeka Eleni , Sympardi Styliani , Papanikolaou Ilias , Koutsodimitropoulos Ioannis , Tzavara Vasiliki , Adamis Georgios , Tsiakos Konstantinos , Koulouras Vasilios , Mouloudi Eleni , Antoniadou Eleni , Vlachogianni Gykeria , Anisoglou Souzana , Markou Nikolaos , Koutsoukou Antonia , Panagopoulos Periklis , Milionis Haralampos , Dalekos George N. , Kyprianou Miltiades , Giamarellos-Bourboulis Evangelos J.
Published: September 2024

OBJECTIVES:

It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes.

DESIGN:

Retrospective analysis of data from prospective clinical studies.

SETTING:

Greek ICUs and Internal Medicine departments.

PATIENTS AND INTERVENTIONS:

We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality.

MEASUREMENTS AND MAIN RESULTS:

The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, β was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern.

CONCLUSIONS:

A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.
Survey of patient experience and management of vasomotor symptoms due to menopause from the PatientsLikeMe community
Authors: Shepherd Jessica A. , Shiozawa Aki , Schild Arianne L. , Singh Deepshikha , Mancuso Shayna A.
Published: September 2024

Objective

This study aimed to describe menopause and treatment experiences of women with vasomotor symptoms due to menopause in the United States.

Methods

A cross-sectional survey was administered to women 40‐65 years of age recruited from PatientsLikeMe, a dedicated online platform for patients.

Results

A total of 196 women (mean age 55.7 years; 81.2% White) completed the survey and were included in the analyses. The majority (87.2%) reported experiencing bothersome symptoms; 54.3% (100/184) had daytime hot flashes, and 59.2% (109/184) had nighttime sweats and hot flashes, up to 5 times per day on average. Mean postmenopause duration was 10.8 years. Although most (68.5%, 126/184) reported having vasomotor symptoms for less than 5 years, some (14.1%, 26/184) had symptoms for more than a decade. Only 35.2% (69/196) were treated for their symptoms; the most frequently reported prescription treatment was hormone therapy (58%; 40/69), which was administered for less than 3 years in most cases (67.5%, 27/40). Although women were generally satisfied with their interactions with healthcare providers, 23.0% reported inadequate support. Sleep, personal relationships, and physical, emotional, and mental well-being were the most affected by vasomotor symptoms. Healthcare professionals with training in women's health were the most valued resource for dealing with the symptoms associated with menopause.

Conclusions

Not all women with symptoms were treated. In those whose concerns were addressed by providers, a reluctance to pursue treatment was still observed. A need persists to ensure that this population has the resources and support needed to effectively manage symptoms.
HAF prevents hepatocyte apoptosis and progression to MASH and HCC through transcriptional regulation of the NF-κB pathway
Authors: Acuña-Pilarte Karen , Reichert Ethan C. , Green Yangsook Song , Halberg Lily M.-T. , Golkowski Martin , Maguire Kathleen M. , Mimche Patrice N. , Kamdem Severin Donald , Hu Po-An , Wright Jillian , Ducker Gregory S. , Voth Warren P. , O’Connell Ryan M. , McFarland Sydney A. , Egal Erika Said Abu , Chaix Amandine , Summers Scott. A. , Reelitz Jordan W. , Maschek John Alan , Cox James E. , Evason Kimberley J. , Koh Mei Yee
Published: September 2024

Background and Aims:

HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction–associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor (HAF) (SART1

+/−) spontaneously develop MASH-HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear.

Approach and Results:

We generated SART1-floxed mice, which were crossed with mice expressing Cre recombinase within hepatocytes (Alb-Cre; hepS−/−) or myeloid cells (LysM-Cre, macS−/−). HepS
−/− mice (both male and female) developed HCC associated with profound inflammatory and lipid dysregulation, suggesting that HAF protects against HCC primarily within hepatocytes. HAF-deficient hepatocytes showed decreased P-p65 and P-p50 in many components of the NF-κB pathway, which was recapitulated using HAF small interfering RNA in vitro. HAF depletion also triggered apoptosis, suggesting that HAF protects against HCC by suppressing hepatocyte apoptosis. We show that HAF regulates NF-κB activity by regulating the transcription of TRADD and RIPK1. Mice fed a high-fat diet showed marked suppression of HAF, P-p65, and TRADD within their livers after 26 weeks but showed profound upregulation of these proteins after 40 weeks, implicating deregulation of the HAF-NF-κB axis in the progression to MASH. In humans, HAF was significantly decreased in livers with simple steatosis but significantly increased in HCC compared with normal liver.

Conclusions:

HAF is a novel transcriptional regulator of the NF-κB pathway and is a key determinant of cell fate during progression to MASH and MASH-HCC.
The Effect of Reiki on the Self-Efficacy, Death Anxiety, and Sleep Quality of Patients Diagnosed With Chronic Obstructive Pulmonary Disease
Authors: Ünal Aslan Kevser Sevgi , Çetinkaya Funda
Published: September 2024

Reiki has been used for various medical problems. The present study aims to determine the effects of Reiki therapy on the self-efficacy, death anxiety, and sleep quality of patients diagnosed with COPD. The present used a quasi-experimental model with a pretest-posttest control group. The subjects (n = 75) were recruited from a hospital in Turkey, between February and June 2019. Subjects were then assigned to Reiki (n = 39) and placebo (n = 36) groups. In this study, it was determined that there was a statistically significant difference in the mean scores of self-efficacy, death anxiety, and sleep quality between the Reiki and placebo groups (P < .05).These results suggest that Reiki exercise increased the self-efficacy and sleep quality levels and decreased the death anxiety.
Do Botulinum Toxin Injections for Upper Face Rejuvenation and Lateral Canthal Rhytids Have Unintended Effects on Tear Production?
Authors: Yao Anthony , Malhotra Raman
Published: September 2024

Purpose:

To report the influence of botulinum toxin A (BoNTA) injections on basal tear production, as measured by Schirmer’s test with anesthesia in patients seeking eyelid surgery.

Methods:

A retrospective cohort of patients requesting esthetic eyelid surgery reviewed by a single clinician between January 2021 to April 2024, assessed with Schirmer’s test with anesthesia. Demographic data, history of BoNTA treatment in the periocular region, ocular surface disease index dry eye symptom frequency, and requirement for ocular lubricants were recorded. Patients with no history of BoNTA were designated as group 1. Patients with a positive recent history of periocular BoNTA were designated as group 2. The proportions of eyes with Schirmer’s test with anesthesia (basal tear production) test result <5 mm (“low”), 5 to 9 mm (“borderline”), and ≥10 mm (“normal”) were compared between groups.

Results:

Seven hundred twenty-two eyes (361 patients) were assessed, of which 670 eyes (335 patients) met the inclusion criteria. Mean age was 55.1 (range, 17–93) years, with 71.3% female. Schirmer’s data in group 1 were “low” at 32.9%, “borderline” at 26.4%, and “normal” at 40.7%. In contrast, group 2 had significantly lower results (P ≤ 0.05), with readings “low” at 48.3%, “borderline” at 26.7%, and “normal” at 25.0%. However, there were no significant differences between groups in ocular surface disease index symptom frequency scores or ocular lubricant requirements.

Conclusions:

Patients who had received BoNTA injections had significantly lower basal tear production compared with patients who had never received BoNTA. Esthetic BoNTA treatment may be associated with an unintended effect of decreased basal tear production and subsequent risk of dry eye.
Non-IgE-mediated drug-induced hypersensitivity reactions in pediatrics
Authors: Chow Timothy G. , Muzaffar Anum F. , Alvarez-Arango Santiago
Published: September 2024

Purpose of review

Despite their prevalence and potential severity, non-IgE-mediated drug-induced hypersensitivity reactions (DHRs) are under-researched and poorly defined, particularly in children. Presentations range from mild cutaneous reactions to severe systemic diseases, with pathophysiological mechanisms and reliable diagnostic markers not well established. The lack of validated tests often leads to permanent drug restrictions, reliance on second-line drugs, and increased costs. Focusing on recent advancements and areas needing further research, this review aims to enhance children's recognition, diagnosis, and management of non-IgE-mediated DHRs.

Recent findings

Recent studies have enhanced the understanding of immediate and delayed non-IgE-mediated drug reactions. Key findings include the Mas-related G protein-coupled receptor X2 in mast cells and the identification of HLA alleles linked to severe cutaneous adverse reactions, such as Stevens–Johnson syndrome and toxic epidermal necrolysis. Improved diagnostic techniques, including skin testing, show promise in identifying immediate and delayed non-IgE DHRs. Additionally, research highlights the impact of cofactors, drug metabolites, and co-infections on these DHRs and explores potential biomarkers for predicting reaction severity.

Non-IgE-mediated DHRs are a significant cause of morbidity and treatment changes in pediatric patients. Recent research underscores their clinical presentations and mechanisms, paving the way for more precise diagnostic and therapeutic strategies to improve patient outcomes.
Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials
Authors: Lin Lujie , Zhang Mingxiao , Xie Huijuan , Yang Min , Zhu Tong , Yang Junxuan , Yang Bin , Li Hua
Published: September 2024

Background

Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis.

Objective

The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date.

Methods

An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity.

Results

Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01] while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment.

Conclusions

SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.
Perception and control of a virtual body in immersive virtual reality for rehabilitation
Authors: Donegan Tony , Sanchez-Vives Maria V.
Published: September 2024

Purpose of review

This review explores recent advances in using immersive virtual reality to improve bodily perception and motor control in rehabilitation across musculoskeletal and neurological conditions, examining how virtual reality's unique capabilities can address the challenges of traditional approaches. The potential in this area of the emerging metaverse and the integration of artificial intelligence in virtual reality are discussed.

Recent findings

In musculoskeletal rehabilitation, virtual reality shows promise in enhancing motivation, adherence, improving range of motion, and reducing kinesiophobia, particularly postsurgery. For neurological conditions like stroke and spinal cord injury, virtual reality's ability to manipulate bodily perceptions offers significant therapeutic potential, with reported improvements in upper limb function and gait performance. Balance and gait rehabilitation, especially in older adults, have also seen positive outcomes. The integration of virtual reality with brain-computer interfaces presents exciting possibilities for severe speech and motor impairments.

Current research is limited by small sample sizes, short intervention durations, and variability in virtual reality systems. Future studies should focus on larger, long-term trials to confirm findings and explore underlying mechanisms. As virtual reality technology advances, its integration into rehabilitation programs could revolutionize treatment approaches, personalizing treatments, facilitating home training, and potentially improving patient outcomes across a wide variety of conditions.
Individual quality and environmental factors interact to shape reproduction and survival in a resident bird of prey
Authors: Bühler Roman , Riecke Thomas V. , Schalcher Kim , Roulin Alexandre , Almasi Bettina
Published: September 2024

Investigating among-individual differences in reproductive success and survival is essential for understanding eco-evolutionary processes. We used 5 years of demographic data from 556 breeding barn owls (
Tyto alba
) to estimate associations between intrinsic and extrinsic covariates on survival and reproduction throughout the annual cycle. As males and females have distinct roles in reproduction, environmental conditions and individual quality may be differentially linked to their fitness at different time points. Males breeding early and inhabiting prey-rich areas experienced higher reproductive success but faced greater reproductive costs. Indeed, the number of offspring a male cared for was negatively associated with his body condition and survival. However, our results indicate that these influences can be mitigated in males experiencing favourable post-breeding environmental conditions. For female owls, early breeding and high food availability during the breeding period were linked with increased reproductive success. Prey availability during incubation and higher reproductive output were associated with higher survival into the next breeding period in females. Unlike males, females did not exhibit obvious trade-offs between reproductive success and survival. Our research demonstrates trade-offs between fecundity and survival, and that females paired with males able to provide sufficient food experience higher survival and reproduction.
Dynamic effects of thermal acclimation on chytridiomycosis infection intensity and transmission potential in
Xenopus laevis
Authors: Noelker James E. , Abreu Ruozzi Vitoria , Spengler Kyle D. , Craig Hunter M. , Raffel Thomas R.
Published: September 2024

The pandemic amphibian pathogen
Batrachochytrium dendrobatidis
(Bd) can cause more severe infections with variable temperatures owing to delays in host thermal acclimation following temperature shifts. However, little is known about the timing of these acclimation effects or their consequences for Bd transmission. We measured how thermal acclimation affects Bd infection in
Xenopus laevis
, using a timing-of-exposure treatment to investigate acclimation effect persistence following a temperature shift. Consistent with a delay in host acclimation, warm-acclimated frogs exposed to Bd immediately following a temperature decrease (day 0) developed higher infection intensities than frogs already acclimated to the cool temperature. This acclimation effect was surprisingly persistent (five weeks). Acclimation did not affect infection intensity when Bd exposure occurred one week after the temperature shift, indicating that frogs fully acclimated to new temperatures within 7 days. This suggests that acclimation effect persistence beyond one week post-exposure was caused by carry-over from initially high infection loads, rather than an extended delay in host acclimation. In a second experiment, we replicated the persistent thermal acclimation effects on Bd infection but found no acclimation effects on zoospore production. This suggests that variable temperatures consistently exacerbate individual Bd infection but may not necessarily increase Bd transmission.
TMPRSS6 cleaves KCNE1 and causes arrhythmias in iron overload disease
Authors: Peischard Stefan , Kastl Philipp , Goerges Gunnar , Schreiber Julian A. , Verkerk Arie O. , Wilders Ronald , Disse Paul , Hornung Isabelle , Klingmüller Ursula , Steinbicker Andrea U. , Rauner Martina , Spasić Maja Vujić , Rosenbauer Frank , Meuth Sven , Budde Thomas , Pedersen Per A. , Jepps Thomas A.Q. , Jespersen Thomas , Strutz-Seebohm Nathalie , Seebohm Guiscard
Published: September 2024

Iron storage disease is associated with cardiovascular manifestations, including various forms of cardiac arrhythmias of unknown origin. In this study, cardiac arrhythmias associated with iron overload were investigated in human iPSC-derived cardiomyocytes (hiPSC-CM) and hiPSC-derived sinus node-like pacemaker cells. Among other effects, iron overload leads to an increase in the plasma membrane-anchored protease TMPRSS6. TMPRSS6 cleaves the auxiliary subunit KCNE1 N-terminally and thus modulates the function of both the IKs(KCNQ1/KCNE1 current) and the If(HCN4/KCNE1) ion channels. Furthermore, TMPRSS6 induces a reduction of electric field potential (EFP) count and increased duration in hiPSC-derived ventricular-like cells and in hiPSC-derived pacemaker-like cells. In accordance with thesein vitrogenerated results, TMPRSS6-mediated interactions show pro-arrhythmic effectsin silico. Therefore, the TMPRSS6 - KCNE1-KCNQ1 and TMPRSS6 - KCNE1-HCN4 cascades may represent new clinically relevant pro-arrhythmic mechanisms in iron overload diseases.
A novel biomechanical model of the mouse forelimb predicts muscle activity in optimal control simulations of reaching movements
Authors: Gilmer Jesse I. , Coltman Susan K. , Cuenu Geraldine , Hutchinson John R. , Huber Daniel , Person Abigail L. , Al Borno Mazen
Published: September 2024

Mice are key model organisms in neuroscience and motor systems physiology. Fine motor control tasks performed by mice have become widely used in assaying neural and biophysical motor system mechanisms. Although fine motor tasks provide useful insights into behaviors which require complex multi-joint motor control, there is no previously developed physiological biomechanical model of the adult mouse forelimb available for estimating kinematics nor muscle activity or kinetics during behaviors. Here, we developed a musculoskeletal model based on high-resolution imaging of the mouse forelimb that includes muscles spanning the neck, trunk, shoulder, and limbs. Physics-based optimal control simulations of the forelimb model were used to estimatein vivomuscle activity present when constrained to the tracked kinematics during reaching movements. The activity of a subset of muscles was recorded and used to assess the accuracy of the muscle patterning in simulation. We found that the synthesized muscle patterning in the forelimb model had a strong resemblance to empirical muscle patterning, suggesting that our model has utility in providing a realistic set of estimated muscle excitations over time when given a kinematic template. The strength of the similarity between empirical muscle activity and optimal control predictions increases as mice performance improves throughout learning of the reaching task. Our computational tools are available as open-source in the OpenSim physics and modeling platform. Our model can enhance research into limb control across broad research topics and can inform analyses of motor learning, muscle synergies, neural patterning, and behavioral research that would otherwise be inaccessible.

NEW & NOTEWORTHY

Investigations into motor planning and execution lack an accurate and complete model of the forelimb, which could bolster or expand on findings. We sought to construct such a model using high detail scans of murine anatomy and prior research into muscle physiology. We then used the model to predict muscle excitations in a set of reaching movements and found that it provided accurate estimations and provided insight into an optimal-control framework of motor learning.
A three-dimensional immunofluorescence atlas of the brain of the hackled-orb weaver spider,Uloborus diversus
Authors: Artiushin Gregory , Corver Abel , Gordus Andrew
Published: September 2024

Spider orb-web building is a captivating, rare example of animal construction, whose neural underpinnings remain undiscovered. An essential step in understanding the basis of this behavior is a foundational mapping of the spider’s neuroanatomy, which has thus far been primarily studied using non-web building species. We created a three-dimensional atlas for the hackled orb-weaver,Uloborus diversus, based on immunostaining for the presynaptic component, synapsin, in whole-mounted spider synganglia. Aligned to this volume, we examined the expression patterns of neuronal populations representing many of the classical neurotransmitter and neuromodulators, as well as a subset of neuropeptides – detailing immunoreactivity in an unbiased fashion throughout the synganglion, revealing co-expression in known structures, as well as novel neuropils not evident in prior spider works.

This optically-sliced, whole-mount atlas is the first of its kind for spiders, representing a substantive addition to knowledge of brain anatomy and neurotransmitter expression patterns for an orb-weaving species.
Maturation of human cardiac organoids enables complex disease modelling and drug discovery
Authors: Pocock Mark , Reid Janice D. , Robinson Harley R. , Charitakis Natalie , Krycer James R. , Foster Simon R. , Fitzsimmons Rebecca L. , Lor Mary , Tuano Natasha , Howden Sara , Vlahos Katerina , Watt Kevin I. , Piers Adam , Voges Holly K. , Fortuna Patrick R.J. , Rae James , Parton Robert G. , Konstantinov Igor E. , Weintraub Robert G. , Elliott David , Ramialison Mirana , Porrello Enzo R. , Mills Richard J. , Hudson James E.
Published: September 2024

Cardiac maturation is an important developmental phase culminating in profound biological and functional changes to adapt to the high demand environment after birth1,2. Maturation of human pluripotent stem cell-derived human cardiac organoids (hCO) to more closely resemble human heart tissue is critical for understanding disease pathology. Herein, we profile human heart maturationin vivo3to identify key signalling pathways that drive maturation in hCOs4,5. Transient activation of both the 5’ AMP-activated kinase (AMPK) and estrogen-related receptor (ERR) promoted hCO maturation by mimicking the increased functional demands of post-natal development. hCOs cultured under these directed maturation (DM) conditions (DM-hCOs) display robust transcriptional maturation including increased expression of mature sarcomeric and oxidative phosphorylation genes resulting in enhanced metabolic capacity. DM-hCOs have functionally mature properties such as sarcoplasmic reticulum-dependent calcium handling, accurate responses to drug treatments perturbing the excitation-coupling process and ability to detect ectopy CASQ2 and RYR2 mutants. Importantly, DM- hCOs permit modelling of complex human disease processes such as desmoplakin (DSP) cardiomyopathy, which is driven by multiple cell types. Subsequently, we deploy DM-hCOs to demonstrate that bromodomain extra-terminal inhibitor INCB054329 rescues theDSPphenotype. Together, this study demonstrates that recapitulatingin vivodevelopment promotes advanced maturation enabling disease modelling and the identification of a therapeutic strategy forDSP-cardiomyopathy.
Inter- and intra-tumor heterogeneous immune presentation in primary uterine carcinosarcoma determined by digital spatial profiling
Authors: Li Ying-Xuan , Lin Wei-Chou , Chen Ko-Chen , Chang Wen-Chun , Wu Chin-Jui , Wei Lin-Hung , Huang Ruby Yun-Ju , Sheu Bor-Ching
Published: September 2024

Uterine carcinosarcoma (UCS) is a rare gynecologic cancer with unfavorable prognosis. Its biphasic histologic components are known to associated with outcomes. Dissecting the tumor heterogeneity within UCS is crucial to discover molecular biomarkers for patient stratification. The aim of this study was to utilize spatial profiling technology to analyze immune presentation in different histological components within UCS tumors. The study included 23 UCS patients whose tumor sections were subjected to nanoString GeoMx Digital Spatial Profiling (DSP) to profile 30 immune-related proteins in 491 segments. We identified distinct cluster-labeled subtypes showing varied immune marker expressions. The immune presentations within the carcinoma and sarcoma components showed significant differences. Markers indicating M2 macrophages (CD45+CD163+) and epithelial-mesenchymal transition (EMT) (SMA, fibronectin) were highly expressed in the sarcoma components. The immune presentation subtypes within each histological component also differed between patients with recurrence in 5 years and without recurrence over 5 years. The cluster-labeled subtype with high Neutrophil/PMN-MDSC marker expression (CD66b) was associated with longer survival, whereas the subtype with high NK cell marker expressions (CD56) was linked to poor prognosis. Our result suggested that immune features within the carcinoma component of UCS tumors would determine patient outcomes and should be considered as a strategy for patient stratification.