bluuebunny/crossref_metadata_2025 huggingface dataset:
NVL-655 Is a Selective and Brain-Penetrant Inhibitor of Diverse ALK-Mutant Oncoproteins, Including Lorlatinib-Resistant Compound Mutations
Authors: Lin Jessica J. , Horan Joshua C. , Tangpeerachaikul Anupong , Swalduz Aurélie , Valdivia Augusto , Johnson Melissa L. , Besse Benjamin , Camidge D. Ross , Fujino Toshio , Yoda Satoshi , Nguyen-Phuong Linh , Mizuta Hayato , Bigot Ludovic , Nobre Catline , Lee Jii Bum , Yu Mi Ra , Mente Scot , Sun Yuting , Kohl Nancy E. , Porter James R. , Shair Matthew D. , Zhu Viola W. , Felip Enriqueta , Cho Byoung Chul , Friboulet Luc , Hata Aaron N. , Pelish Henry E. , Drilon Alexander
Published: September 2024

Three generations of tyrosine kinase inhibitors (TKI) have been approved for anaplastic lymphoma kinase (ALK) fusion–positive non–small cell lung cancer. However, none address the combined need for broad resistance coverage, brain activity, and avoidance of clinically dose-limiting TRK inhibition. NVL-655 is a rationally designed TKI with >50-fold selectivity for ALK over 96% of the kinome tested. In vitro, NVL-655 inhibits diverse ALK fusions, activating alterations, and resistance mutations, showing ≥100-fold improved potency against ALKG1202R single and compound mutations over approved ALK TKIs. In vivo, it induces regression across 12 tumor models, including intracranial and patient-derived xenografts. NVL-655 inhibits ALK over TRK with 22-fold to >874-fold selectivity. These preclinical findings are supported by three case studies from an ongoing first-in-human phase I/II trial of NVL-655 which demonstrate preliminary proof-of-concept clinical activity in heavily pretreated patients with ALK fusion–positive non–small cell lung cancer, including in patients with brain metastases and single or compound ALK resistance mutations.

Significance: By combining broad activity against single and compound ALK resistance mutations, brain penetrance, and selectivity, NVL-655 addresses key limitations of currently approved ALK inhibitors and has the potential to represent a distinct advancement as a fourth-generation inhibitor for patients with ALK-driven cancers.
Figure 4 from Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer
Authors: Murayama Takahiko , Mahadevan Navin R. , Meador Catherine B. , Ivanova Elena V. , Pan Yuqiao , Knelson Erik H. , Tani Tetsuo , Nakayama Jun , Ma Xueying , Thai Tran C. , Hung Yin P. , Kim William , Watanabe Hideo , Cai Kathy Q. , Hata Aaron N. , Paweletz Cloud P. , Barbie David A. , Cañadas Israel
Published: September 2024

TREX1 depletion resensitizes resistant SCLC tumors to chemotherapy. A, Schematic of the method used to establish cisplatin-resistant H82 (H82-CispR) cells. B, Expression levels of TREX1 in H82 and H82-CispR (Scr and sgTREX1) cells were compared by immunoblotting. C, Expression levels of IFNB and IFIT1 genes were compared between Scr and sgTREX1 H82-CispR cells by qPCR (mean ± SEM; n = 3). D, Growth curves of the indicated cells treated with DMSO (Left) or 1.0-µmol/L cisplatin (Right) were compared (mean ± SEM; n = 3). E, Tumor growth curves of Scr and sgTREX1 H82-CispR tumors (n = 5), treated with 5-mg/kg cisplatin, were compared. F, Tumor growth curves of Scr and sgTREX1 H69AR tumors (n = 6), treated with 5-mg/kg cisplatin, were compared. G, Expression levels of the IFNB gene were compared between shCtrl and shTREX1 H1048 cells treated w/wo DOX (mean ± SEM; n = 3). H, Tumor growth curves of shCtrl and shTREX1 H1048 tumors (n = 6), treated with 5-mg/kg cisplatin, were compared. I, Schematic model of antitumor effects caused by TREX1 depletion. Data represent mean ± SEM. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by unpaired Student t test (C, E, and F) and one-way ANOVA followed by Dunnett’s multiple comparison test (D), and two-way ANOVA followed by Tukey’s multiple comparison test (G and H). (I, Created with BioRender.com.)
Supplementary Figure S3 from A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170)
Authors: Maldonado Edward , Rathmell W. Kimryn , Shapiro Geoffrey I. , Takebe Naoko , Rodon Jordi , Mahalingam Devalingam , Trikalinos Nikolaos A. , Kalebasty Arash R. , Parikh Mamta , Boerner Scott A. , Balido Celene , Krings Gregor , Burns Timothy F. , Bergsland Emily K. , Munster Pamela N. , Ashworth Alan , LoRusso Patricia , Aggarwal Rahul R.
Published: September 2024

Supplementary Figure S3 shows all 8 patients with H3K36me3 IHC analysis. (A) Cohort A: Other Solid Tumor. (B) Cohort B: ccRCC. Images are at 40x power. Of note, the portal did not allow for uploading of a TIFF file alone as a "supplemental data" file, so the image included in this document is a TIFF file. We can easily provide the TIFF file if needed as well.
Table 1 from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Baseline characteristics and demographics
Supplementary Table 2 from ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N.
Published: September 2024

Supplementary Table 2. TEAEs Occurring in at Least 15% of Dose Escalation Patients
Yao Syndrome: An Overview of Genotypic Associations, Clinical Manifestations, Diagnosis, and Treatment
Authors: Khalid Ayesha , Kaell Alan
Published: September 2024

Background: Yao syndrome (YAOS) is a rare systemic autoinflammatory disorder (AID) of the innate immune system. It was recently categorized as genetically transitional disease (GTD) and is associated with NOD2 variants located at multiple NOD2 gene loci. Unlike most other periodic fever syndromes, the estimated disease prevalence is 1–10/100,000 with a predominance for females and white adult population. In this review, we aimed to provide a detailed analysis of different aspects of this syndrome to help better understand the underlying pathogenesis and incorporate the current evidence-based medicine published to diagnose and manage these patients. Summary: We conducted literature search on YAOS from 2011 to 2024 using PubMed, Embase, and Scopus databases. Thirty-two studies were included in our narrative review. A descriptive analysis was performed of both Yao and non-Yao authored records to embrace the syndrome reported from all investigators and assess differences and similarities. The most reported gene variant is the homozygous IVS8+158 followed by compound heterozygous IVS8+158 and R702W. Mean age of disease onset is between 36 and 42 years. The mean age of disease diagnosis is between 40 and 45 years with a variable disease duration. Fever is the most commonly reported symptom followed by musculoskeletal, gastrointestinal symptoms and dermatitis. On laboratory workup, patients have elevated levels of erythrocyte sedimentation rate, C-reactive protein, and serum ferritin with negative autoantibody workup. Arthritic symptoms in YAOS patients have a positive response to sulfasalazine and glucocorticoids, while nonsteroidal anti-inflammatory drugs and colchicine produce minimal response. Anti-IL1 and anti-IL6 agents (canakinumab, anakinra, and tocilizumab) are effective treatment modalities. Key Messages: The evolving concept and acceptance of GTD will hopefully further our understanding about this SAID and similar disorders. We suggest developing a registry of patients with YAOS to keep track of expanding data on this subject. It is important to understand various aspects of YAOS including genetic and environmental factors, differential diagnosis, clinical manifestations, laboratory findings, and treatment options available to diagnose and manage these patients appropriately and timely.
Clinical Characteristics, Current Treatment Options, Potential Mechanisms, Biomarkers, and Therapeutic Targets in Avascular Necrosis of Femoral Head
Authors: Khanchandani Prakash , Narayanan Aswath , Naik Ashwin A. , Kannan Vishnu , Pradhan Sai Sanwid , Srimadh Bhagavatham Sai Krishna , Pulukool Sujith kumar , Sivaramakrishnan Venketesh
Published: September 2024

Avascular necrosis of femoral head (AVNFH) is a debilitating disease of the young, affecting the quality of life significantly and eventually leading to total hip replacement surgery. The disease is diagnosed clinico-radiologically and MRI is the investigation of choice to diagnose the early stages of the disease. There is neither an early biomarker for detection nor is there a permanent cure for the disease and most of the patients are managed with various combinations of surgical and medical management protocols. In this review, we comprehensively address the etiopathogenesis, clinical characteristics, therapeutic procedures, bone characteristics, histopathology, multi-omic studies, finite element modeling, and systems analysis that has been performed in AVNFH. The etiology includes various factors that compromise the blood supply to the femoral head which also includes contributions by environmental and genetic factors. Multi-omic analysis has shown an association of deregulated pathways with the disease. The cell types involved include mesenchymal stem cells, osteoblasts, osteoclasts, endothelial and immune cells. Biochemical, hematological, histopathology, IHC, and other bone remodeling and degradation marker studies have been performed. A systems analysis using multi-omic data sets from published literature was carried out, the relevance of which is discussed to delineate potential mechanisms in etiopathogenesis, diagnosis, and effective management of this debilitating disease.
Approach to Acute Dizziness/Vertigo in the Emergency Department: Selected Controversies Regarding Specialty Consultation
Authors: Puissant Madeleine M. , Giampalmo Susan , Wira Charles R. , Goldstein Joshua N. , Newman-Toker David E.
Published: September 2024

Acute dizziness and vertigo are common emergency department presentations (≈4% of annual visits) and sometimes, a life-threatening diagnosis like stroke is missed. Recent literature reviews the challenges in evaluation of these symptoms and offers guidelines for diagnostic approaches. Strong evidence indicates that when well-trained providers perform a high-quality bedside neurovestibular examination, accurate diagnosis of peripheral vestibular disorders and stroke increases. However, it is less clear who can and should be performing these assessments on a routine basis. This article offers a focused debate for and against routine specialty consultation for patients with acute dizziness or vertigo in the emergency department as well as a potential path forward utilizing new portable technologies to quantify eye movements.
Self-Reproduction and Evolution in Cellular Automata: 25 Years After Evoloops
Authors: Sayama Hiroki , Nehaniv Chrystopher L.
Published: September 2024

The year 2024 marks the 25th anniversary of the publication of evoloops, an evolutionary variant of Chris Langton’s self-reproducing loops, which proved constructively that Darwinian evolution of self-reproducing organisms by variation and natural selection is possible within deterministic cellular automata. Over the last few decades, this line of Artificial Life research has since undergone several important developments. Although it experienced a relative dormancy of activity for a while, the recent rise of interest in open-ended evolution and the success of continuous cellular automata models have brought researchers’ attention back to how to make spatiotemporal patterns self-reproduce and evolve within spatially distributed computational media. This article provides a review of the relevant literature on this topic over the past 25 years and highlights the major accomplishments made so far, the challenges being faced, and promising future research directions.
Digital Technologies and Atrocity Risks
Authors: Pawnday Savita
Published: September 2024

From a practitioner’s perspective the intervention explores how digital technologies have enhanced the capacities of policy-makers in anticipating and responding to atrocity crimes including through development and access to sophisticated technologies to collect and verify evidence of crimes for justice and accountability. Digital technologies have also provided perpetrators with enhanced tools to target populations with greater precision and commit atrocities against them. The intervention argues that the harm perpetuated by digital technologies can be mitigated by holding developers of these technologies accountable for creating operating environments that are safe and by naming and shaming governments that use new technologies to target populations.
Review of the family Vanhorniidae (Hymenoptera: Proctotrupoidea), with the description of two new species
Authors: ABE JUNTA , YAMAGISHI KENZO , KONISHI KAZUHIKO
Published: September 2024

World species of the genus Vanhornia, the only member of Vanhorniidae, are reviewed and six species are recognized. Two new species, V. formosana sp. nov. from Taiwan and V. hikosanensis sp. nov. from Japan, are described. The record of V. eucnemidarum from South Korea is invalidated. New distributional records are reported for V. quizhouensis from Laos and V. yurii from Japan and South Korea. A key to species of Vanhornia is provided with photographs of all species.
First record of subgenus Corynopus Lepeletier and Brullé, 1835 (Genus Rhopalum Stephens, Hymenoptera: Crabronidae: Crabronini) from India: a new species and a key to Asian species of the subgenus
Authors: SAINI VARUN , DEY DEBJANI
Published: September 2024

The subgenus Corynopus Lepeletier de Saint Fargeau and Brullé, 1835 of the genus Rhopalum Stephens, 1829 is recorded for the first time from India. A new species, viz., Rhopalum (Corynopus) chettalicum, (India: Karnataka) is described. A key and the checklist of all Asian species of the subgenus Corynopus are provided.
Extinguishing the Fiery Skies: The History and Modern Prospects of Lightning Suppression within Thunderstorms
Authors: Stepanian Phillip M. , Williams Earle R.
Published: September 2024

It has been over 75 years since the concept of directly suppressing lightning by modifying thunderstorm cloud processes was first proposed as a technique for preventing wildfire ignitions. Subsequent decades produced a series of successful field campaigns that demonstrated several techniques for interrupting storm electrification, motivated in part by the prospect of protecting Apollo-era rocket launches from lightning strike. Despite the technical success of these research programs, funding and interest diminished until the final field experiment in 1975 marked the last large-scale activity toward developing lightning prevention technology. Having lost widespread awareness over the ensuing 50 years, these pioneering efforts in experimental cloud physics have largely been forgotten, and this approach for mitigating lightning hazards has fallen into obscurity. At the present day, risks from lightning-ignited wildfires to lives, property, and infrastructure are once again a major topic of concern. Similarly, the rapid development of an emerging commercial space sector is placing new demands on airspace management and launch scheduling. These modern challenges may potentially be addressed by a seemingly antiquated concept—lightning suppression—but considerations must be made to understand the consequences of deploying this technology. Nonetheless, the possible economic, environmental, and societal benefits of this approach merit a critical reevaluation of this hazard mitigation technology in the current era.
Hypophysitis and central nervous system involvement in association with Sjögren’s syndrome along with hypoparathyroidism: a case report
Authors: Yum Jungyon , Lee Sang-Won , Rhee Yumie , Heo Kyoung
Published: September 2024

Background

Patients with autoimmune diseases can develop multiple autoimmune diseases over a long period of time, and the presence of more than one autoimmune disease in a single patient is defined as polyautoimmunity. Polyautoimmunity may be clinical evidence that autoimmune diseases share similar immunological mechanisms.

Case presentation

We report a 30-year-old woman with a unique combination of autoimmune diseases predominantly affecting the central nervous system, with hypoparathyroidism, hypophysitis, medulla involvement, and pons and temporal lobe involvement associated with primary Sjögren's syndrome (pSS), occurring independently over a long period. The patient who had a history of muscle cramps and one seizure incident, presented with vomiting and blurred vision. She was diagnosed with hypophysitis and hypoparathyroidism with calcifications in the basal ganglia and cerebellum. She recovered after four months of corticosteroid treatment for hypophysitis and was started on treatment for hypoparathyroidism. Eight months later, she developed vomiting, hiccups, vertigo, and ataxia with a focal lesion in the medulla. She recovered with immunosuppressive treatment for 2 years. Fifty-eight months after the onset of hypophysitis, she developed diplopia and dry mouth and eyes. MRI showed infiltrative lesions in the left pons and left temporal lobe. Based on positive anti-Sjögren's syndrome-related antigen A antibodies and low unstimulated whole salivary flow rate, pSS was diagnosed. She received corticosteroids and continued mycophenolate mofetil treatment with recovery of neurological symptoms.

Conclusion

This case highlights the need for long-term follow-up to detect autoimmune disease processes involving various organs.
Navigating chronic uncertainty: a theory synthesis for nursing communication in life-limiting illness
Authors: Grant Julie B. , Johnson-Koenke Rachel
Published: September 2024

Background

Despite the proven benefits of early palliative care, patient communication regarding these services remains elusive. Therefore, this paper aims to (a) provide a focused literature review on nurse palliative care communication addressing chronic uncertainty in life-limiting illness (LLI), (b) define the Reconceptualization of Uncertainty in illness Theory and Problematic Integration Theory within a nursing Unitary Caring Science philosophical worldview and, (c) synthesize these theories and literature review into a unique theoretical framework for early palliative care communication in acute care nursing.

Method

Turner’s theory synthesis methodology was combined with a PRISMA-style literature review. The literature search was conducted in July 2023 and updated in May 2024 using EBSCOhost, Pubmed, and PsychINFO databases. A second literature search was undertaken to identify applicable uncertainty theories in chronic or LLIs.

Results

This theory synthesis highlights the interconnectedness of all facets of uncertainty for those living with severe LLI (personal factors, types of uncertainty, and the nursing communicatory process) and conceptualizes uncertainty communication as a series of events happening simultaneously, not simply a cause-and-effect process.

Discussion

The framework resulting from this synthesis encourages nurses’ holistic understanding of the complex nature of uncertainty in LLI, highlights the integral communicatory role nurses have in their patients’ health and wellness, and promotes further nursing-specific communication research. Future research on enabling nurse-initiated early palliative care communication and narrative communication techniques will support patients’ values and dignity throughout more than a single hospital stay but their entire disease trajectory.
Quality indicators for occupational therapy: a scoping review
Authors: Ballmer Thomas , Frey Sara , Petrig Andrea , Gantschnig Brigitte E.
Published: September 2024

Background

Occupational therapists are increasingly asked to demonstrate the effectiveness, appropriateness, and efficiency of their interventions to funding bodies. However, the extent to which this is practiced and the health policy context within which such a practice is situated differs internationally. The aim of this scoping review was to establish which quality indicators are used internationally for this purpose.

Methods

We conducted a scoping review, limiting our search to Europe and the English-speaking world. To search for suitable literature, we used specialized databases from medicine, health sciences, and related fields, including CINAHL Complete and MEDLINE, as well as free internet search via Google. Furthermore, we contacted national occupational therapy associations from several countries asking for access to documents found within this search that were only accessible to association members.

Results

The screening process identified 32 studies and documents from six national contexts. We identified and described process-level indicators, functional outcome indicators, one outcome indicator based on individual goal attainment (the Goal Attainment Scale, or GAS), and PRO-Ergo, a patient-reported experience measure (PREM). There was little information on the use of quality indicators to demonstrate the effectiveness, appropriateness, and efficiency of occupational therapy services to funding bodies in Europe and the English-speaking world that was openly available. The identified process indicators were in most cases not specific to occupational therapy interventions. Functional outcome indicators were highly specific to certain client groups or health conditions and partially appropriate for use in occupational therapy. The GAS was found to be a highly customizable measure which allowed an evaluation on body structure and function levels as well as activity and participation levels. PRO-Ergo was focused on the clients’ subjective view and their experience with occupational therapy interventions.

Conclusions

All identified quality indicators have advantages and disadvantages. Process-level indicators specific to occupational therapy could be a chance to foster the use of best practice methods. GAS and PRO-Ergo seem to be the most versatile assessment, allowing an evaluation on the level of activity and participation. Functional outcome indicators that cover a broad area of client problems may be useful additional quality indicators for some areas of practice.
Patient-reported outcome measures for acute rhinosinusitis in adults and children: a systematic review of the quality of existing instruments
Authors: Baalmann Ann-Kristin , Nestler Sophie , Donhauser Theresa , Apfelbacher Christian , Piontek Katharina
Published: September 2024

Background

Acute rhinosinusitis (ARS) is a self-limiting inflammation of the nose and sinuses caused by viral or bacterial infections that requires primarily symptomatic treatment. Patient-reported outcome measures (PROMs) are suitable tools for the assessment of the effectiveness of remedies for ARS from the patient’s perspective in clinical trials and real-world studies. Data regarding the quality of existing PROMs for ARS are limited.

Purpose

To conduct a systematic review of the quality of existing disease-specific PROMs for use in adults and children with ARS according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology, and to derive recommendations for use of the identified instruments in future clinical studies.

Methods

We systematically searched PubMed, Web of Science and Embase for studies reporting on the development and/or validation of PROMs for ARS. We assessed the methodological quality of each included study, evaluated the quality of measurement properties per PROM and study, and graded the evidence. Based on the overall evidence, we derived recommendations for use of the instruments.

Results

We identified four studies on three PROMs measuring symptoms of ARS and quality of life in adults (Sinonasal Outcome Test-16, SNOT-16; Measurement of Acute Rhinosinusitis, MARS; Rhinosinusitis Quality-of-Life Assessment, RhinoQoL). For ARS in children, we identified two studies on two PROMs measuring symptoms of ARS (Pediatric Rhinosinusitis Symptom Scale, PRSS; Sinus Symptom Questionnaire, S5). Our assessment of measurement properties indicates that all instruments require further validation before they can be unrestrictedly recommended for use in future research (COSMIN category B). In particular, there were no content validity studies for any of the identified instruments, but also data on other important measurement properties, e.g., structural validity, are lacking.

Conclusion

Currently, no PROM for ARS in adults and children can be unrestrictedly recommended based on the evaluation of their quality. Further validation is required for all identified PROMs. Content validation involving patients and experts should be given priority.

Systematic review registration

OSF (https://doi.org/10.17605/OSF.IO/VAP8U).
Exploring the perspectives of health care professionals on digital health technologies in pediatric care and rehabilitation
Authors: Roy Isabelle , Salles Julia , Neveu Erika , Lariviére-Bastien Danaë , Blondin Aurélie , Levac Danielle , Beauchamp Miriam H.
Published: September 2024

Background

Digital health technologies are increasingly used by healthcare professionals working in pediatric hospital and rehabilitation settings. Multiple factors may affect the implementation and use of digital health technologies in these settings. However, such factors have not been identified in a multidisciplinary, pediatric context. The objective of this study was to describe actual use and to identify the factors that promote or hinder the intention to use digital health technologies (mobile learning applications, virtual/augmented reality, serious games, robotic devices, telehealth applications, computerized assessment tools, and wearables) among pediatric healthcare professionals.

Methods

An online survey evaluating opinions, current use, and future intentions to use digital health technologies was completed by 108 professionals at one of Canada’s largest pediatric institutes. Mann-Whitney U tests were used to compare the attitudes of healthcare professionals who intend to increase their use of digital health technologies and those who do not. Linear regression analyses were used to determine predictors of usage success.

Results

Healthcare professionals reported mostly using mobile and tablet learning applications (n = 43, 38.1%), telehealth applications (n = 49, 43.4%), and computerized assessment tools (n = 33, 29.2%). Attitudes promoting the intention to increase the use of digital health technologies varied according to technology type. Healthcare professionals who wished to increase their use of digital health technologies reported a more positive attitude regarding benefits in clinical practice and patient care, but were also more critical of potential negative impacts on patient-professional relationships. Ease of use (β = 0.374; p = 0.020) was a significant predictor of more favorable usage success. The range of obstacles encountered was also a significant predictor (β = 0.342; p = 0.032) of less favorable evaluation of usage success. Specific factors that hinder successful usage are lack of training (β = 0.303; p = 0.033) and inadequate infrastructure (β = 0.342; p = 0.032).

Conclusions

When working with children, incorporating digital health technologies can be effective for motivation and adherence. However, it is crucial to ensure these tools are implemented properly. The findings of this study underscore the importance of addressing training and infrastructure needs when elaborating technology-specific strategies for multidisciplinary adoption of digital health technologies in pediatric settings.
Clinicians’ experience of barriers and facilitators to care delivery of an extracorporeal cardiopulmonary resuscitation service for out-of-hospital cardiac arrest: a qualitative survey
Authors: Eddison Jasper , Millerchip Oscar , Rosenberg Alex , Lewinsohn Asher , Raitt James
Published: September 2024

Background

Out-of-hospital cardiac arrest (OHCA) survival in the UK remains overall poor with fewer than 10% of patients surviving to hospital discharge. Extracorporeal cardiopulmonary resuscitation (ECPR) is a developing therapy option that can improve survival in select patients if treatment begins within an hour. Clinicians' perspectives are a pivotal consideration to the development of effective systems for OHCA ECPR, but they have been infrequently explored. This study investigates clinicians' views on the barriers and facilitators to establishing effective systems to facilitate transport of OHCA patients for in-hospital ECPR.

Methods

In January 2023, Thames Valley Air Ambulance (TVAA) and Harefield Hospital developed an ECPR partnership pathway for conveyance of OHCA patients for in-hospital ECPR. The authors of this study conducted a survey of clinicians across both services looking to identify clear barriers and positive contributors to the effective implementation of the programme. The survey included questions about technical and non-technical barriers and facilitators, with free-text responses analysed thematically.

Results

Responses were received from 14 pre-hospital TVAA critical care and 9 in-hospital clinicians’ representative of various roles and experiences. Data analysis revealed 10 key themes and 19 subthemes. The interconnected themes, identified by pre-hospital TVAA critical care clinicians as important barriers or facilitators in this ECPR system included educational programmes; collectiveness in effort and culture; teamwork; inter-service communication; concurrent activity; and clarity of procedures. Themes from in-hospital clinicians’ responses were distilled into key considerations focusing on learning and marginal gains, standardising and simplifying protocols, training and simulation; and nurturing effective teams.

Conclusion

This study identified several clear themes and subthemes from clinical experience that should be considered when developing and modelling an ECPR system for OHCA. These insights may inform future development of ECPR programmes for OHCA in other centres. Key recommendations identified include prioritising education and training (including regular simulations), standardising a ‘pitstop style’ handover process, establishing clear roles during the cannulation process and developing standardised protocols and selection criteria. This study also provides insight into the feasibility of using pre-hospital critical care teams for intra-arrest patient retrieval in the pre-hospital arena.
The spread of the invasive mosquito Aedes albopictus (Diptera: Culicidae) in Portugal: a first genetic analysis
Authors: Zé-Zé Líbia , Freitas Inês Campos , Silva Manuel , Soares Patrícia , Alves Maria João , Osório Hugo Costa
Published: September 2024

Background

Aedes albopictus, commonly known as the Asian tiger mosquito, has become one of the most invasive mosquito species. Over the last 5 decades, it has been introduced and established in various tropical and temperate regions worldwide. First reported in Europe in 1979 in Albania and later in Italy in 1990, the species is now established in 13 European Union (EU)/European Economic Area (EEA) countries and 337 regions (2023). In Portugal, Ae. albopictus was first detected in the Algarve and Penafiel regions in 2017, followed by Alentejo in 2022 and Lisbon in 2023. This mosquito species poses a significant public health risk as a vector for numerous pathogenic viruses, including dengue, Zika, and chikungunya.

Methods

Aedes albopictus collected in Lisbon in 2023 were analyzed using cytochrome c oxidase I (COX) gene sequencing to understand their genetic relationships.

Results

Our data indicate that the Ae. albopictus mosquito populations detected in three locations in Lisbon in 2023 correspond to recent but distinct introduction events.

Conclusions

Although there has been no local transmission of Aedes-transmitted viruses in mainland Portugal to date, the spread of the mosquito and increased international travel increase the risk of Aedes-borne disease outbreaks. The ongoing spread of Ae. albopictus in the country and the confirmed multiple introductions in new locations raise awareness of the need to monitor mosquito vectors to control and prevent autochthonous Aedes-borne disease outbreaks.

Graphical Abstract
Comparison of multi-parallel quantitative real-time PCRs targeting different DNA regions and detecting soil-transmitted helminths in stool
Authors: Papaiakovou Marina , Cimino Rubén O. , Pilotte Nils , Dunn Julia , Littlewood D. Timothy J. , Williams Steven A. , Krolewiecki Alejandro J. , Mejia Rojelio
Published: September 2024

Background

Soil-transmitted helminths infect an estimated 18% of the world’s population, causing a significant health burden. Microscopy has been the primary tool for diagnosing eggs from fecal samples, but its sensitivity drops in low-prevalence settings. Quantitative real-time polymerase chain reaction (qPCR) is slowly increasing in research and clinical settings. However, there is still no consensus on preferred qPCR targets.

Methods

We aimed to compare soil-transmitted helminth (STH) DNA detection methods by testing naïve stool samples spiked with known quantities of STH eggs and larvae. DNA extracts from spiked samples were tested using independent quantitative realtime PCR (qPCR) assays targeting ribosomal or putative non-protein coding satellite sequences.

Results

For Trichuris trichiura, there was a strong correlation between egg/larvae counts and qPCR results using either qPCR method (0.86 and 0.87, respectively). Strong correlations also existed for A. lumbricoides (0.60 and 0.63, respectively), but weaker correlations were found for Ancylostoma duodenale (0.41 for both assays) and Strongyloides stercoralis (0.48 and 0.65, respectively). No correlation for Necator americanus was observed when testing with either qPCR assay. Both assays had fair-to-moderate agreement across targets when using field-collected stool samples (0.28–0.45, for all STHs), except for S. stercoralis (0.12) with slight agreement.

Conclusions

There is a strong correlation between qPCR results and egg/larvae counts. Our study confirms that qPCR is an effective diagnostic tool, even with low-intensity infections, regardless of the DNA-based diagnostic marker used. However, the moderate agreement between the two different qPCR assays when testing field samples highlights the need to understand the role of these targets in the genome so that the parasite burden can be quantified more accurately and consistently by qPCR.

﻿Graphical abstract
Global patterns of syphilis, gonococcal infection, typhoid fever, paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy from 1990 to 2021: findings from the Global Burden of Disease Study 2021
Authors: Chen Weiye , Chen Yiming , Cheng Zile , Chen Yiwen , Lv Chao , Ma Lingchao , Zhou Nan , Qian Jing , Liu Chang , Li Min , Guo Xiaokui , Zhu Yongzhang
Published: September 2024

Background

Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy.

Methods

Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI.

Results

By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections.

Conclusions

Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts.

Graphical Abstract
Clinical Outcomes and Efficacy of Human Epidermal Growth Factor Receptor 2–Targeted Therapy in Breast Cancer With Uncommon In Situ Hybridization Patterns or Discordant Immunohistochemistry
Authors: Zhang Qianchen , Freeman Jincong Q. , Zhao Fangyuan , Chen Nan , Nanda Rita , Huo Dezheng , Howard Frederick M.
Published: September 2024

PURPOSE

Human epidermal growth factor receptor 2 (HER2)–targeted therapy improves outcomes in HER2+ breast cancer, but efficacy in cases with discordant immunohistochemistry (IHC) and in situ hybridization (ISH) results or with ASCO/College of American Pathologists (CAP) group 2-4 ISH results remains uncertain.

METHODS

This retrospective study included patients from the National Cancer Database diagnosed from 2013 to 2021. Cases were classified as classically HER2+ (HER2/centromeric region of chromosome 17 [CEP17] ratio ≥2 with HER2 copy number ≥4, IHC 2-3+), HER2– (ratio <2, copy number <4, IHC 0-2+), discordant ISH/IHC, or HER2+ with ISH group 2 (ratio ≥2, copy number <4), group 3 (ratio <2, copy number ≥6), or group 4 (ratio <2, copy number ≥4 and <6) per ASCO/CAP guidelines. Adjusted odds ratio (aOR) for pathologic complete response (pCR) for these subgroups receiving HER2-targeted therapy was calculated compared with HER2– controls.

RESULTS

We identified N = 144,013 patients with IHC and dual-probe ISH. Of HER2 IHC 3+ cases (n = 8,579), 8.2%, 2.8%, 4.2%, and 8.8% had ISH categorized as groups 2, 3, 4, and 5 (discordant negative), respectively. Classically, HER2+ (aOR, 2.9 [95% CI, 2.65 to 3.18], P < .001) and group 2 (aOR, 2.38 [95% CI, 1.42 to 3.96], P < .001) treated with HER2-targeted therapy had higher pCR than HER2– controls. Benefit was also seen in group 3 (aOR, 1.63 [95% CI, 1.24 to 2.13], P < .001) and cases with discordant ISH+/IHC– (aOR, 1.61 [95% CI, 1.13 to 2.30], P = .008)—but this was only significant in group 3 cases with copy number ≥8 and discordant ISH+/IHC– cases with HER2/CEP17 ratio ≥3. Group 4 ISH cases and cases with ISH–/IHC+ did not benefit.

CONCLUSION

Patients with ASCO/CAP group 4, discordant ISH–/IHC+ results, and weakly amplified group 3 and discordant ISH+/IHC– have low benefit from HER2 therapy, and alternative approaches for such patients are needed.
Modeling and analysis of COVID-19 spreading based on complex network theory
Authors: Wang R. F. , Chen Y. S. , Liu Y. W. , Ge L. , Liu Y. , Tang M.
Published: September 2024

Complex networks can effectively describe interactions within real-world complex systems. In researches of epidemic spreading, scientists constructed various physical contact networks between individuals on the microscopic scale and the metapopulation networks on the macroscopic scale. These different types of network structures significantly impact the propagation dynamics of epidemic in human society. For instance, population flows in global airline networks influence the speed and arrival time of epidemics across large-scale space. In this paper we review the epidemic spreading models on various network structures, including fully mixed networks, three types of lower-order networks, three types of higher-order networks, metapopulation networks, and multiple strains competitive epidemic spreading models. We also provide an overview of the application of complex network theory in the COVID-19 pandemic, covering topics of prediction, prevention, and control of the epidemic. Finally, we discuss the strengths and limitations of these models and propose perspectives for future research.
Developments in Transfusion Medicine: Pulmonary Transfusion Reactions and Novel Blood Cell Labeling Techniques
Authors: Phelp Philippa G. , van Wonderen Stefan F. , Vlaar Alexander P. J. , Kapur Rick , Klanderman Robert B.
Published: September 2024

Staying updated on advancements in transfusion medicine is crucial, especially in critical care and perioperative setting, where timely and accurate transfusions can be lifesaving therapeutic interventions. This narrative review explores the landscape of transfusion-related adverse events, focusing on pulmonary transfusion reactions such as transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). TACO and TRALI are the leading causes of transfusion-related morbidity and mortality; however, specific treatments are lacking. Understanding the current incidence, diagnostic criteria, pathogenesis, treatment, and prevention strategies can equip clinicians to help reduce the incidence of these life-threatening complications. The review discusses emerging pathogenic mechanisms, including the possible role of inflammation in TACO and the mechanisms of reverse TRALI and therapeutic targets for TACO and TRALI, emphasizing the need for further research to uncover preventive and treatment modalities. Despite advancements, significant gaps remain in our understanding of what occurs during transfusions, highlighting the necessity for improved monitoring methods. To address this, the review also presents novel blood cell labeling techniques in transfusion medicine used for improving monitoring, quality assessment, and as a consequence, potentially reducing transfusion-related complications. This article aims to provide an update for anesthesiologists, critical care specialists, and transfusion medicine professionals regarding recent advancements and developments in the field of transfusion medicine.
The Essential Jill Johnston Reader
Authors: Johnston Jill , Croft Clare
Published: September 2024

Jill Johnston began the 1960s as an influential dance columnist for the Village Voice and by the start of the next decade she was known as a keen observer of postmodern art and lesbian feminist life who challenged how dance, art, and women can and should be seen. The Essential Jill Johnston Reader collects dozens of pieces of her writing from across her career. These writings—many of which appeared in the Village Voice and the New York Times—survey the breadth of her work, braiding together her thinking, writing, and activism. From personal essays, travel writing, and artist profiles to dance and visual art reviews as well as her infamous series of columns for the Voice in which she came out as a lesbian, these pieces demonstrate the evolution of her philosophies and writing style. Illustrating how Johnston drew on lessons from dance to reconsider what it means to be a woman, this collection brings a fascinating and brilliant voice of American arts criticism, radical feminism, and gay liberation back to contemporary audiences.
Cognitive advantages of the livelihood conception in the context of research into the quality of life
Authors: Kałamucka Wioletta
Published: September 2024

The article aims to present cognitive advantages of theoretical conceptions of the quality of life in the context of life quality research. The literature review indicates theoretical foundations of both approaches and problems with the parametrisation of the quality of life. The thematic scope of this notion is deeply embedded in a discourse on welfare and development as it was accepted as a measure of a reasonable economy and the implementation of development processes on a social level. The lack of one, commonly adopted definition produces many research approaches and various ways of measuring. What may prove useful in research into the quality of life is the livelihood conception. It was formed in a scientific milieu at the end of the 1980s and developed both analytically and in operational terms, making it possible to be used in practice, primarily in aid measures for developing countries. It was naturally linked to endogenous development theory, emphasising the importance of a local context. The conception takes account of a broad context of links between living conditions and socio-institutional factors. It also combines them with the results obtained and their evaluation. The livelihood conception is useful in research into occurrences determined by a large dynamic of changes in the form of sudden crises and long-term processes. The framework of this conception allows maintaining a synthetic picture of the quality of life and makes it possible to analyse developments both in the context of opportunities and threats. The conception is a useful tool for identifying possibilities for improvement in the present situation. It combines descriptive and evaluative dimensions of the quality of life being particularly helpful in local-scale research in which geographical factors significantly affect the quality of life. When applying this approach in research, geographers have a chance to be more fully engaged in studying current processes either in the realm of their own discipline or in interdisciplinary teams.
Η μετασχηματίζουσα μάθηση μέσα από την αισθητική εμπειρία στη διαπολιτισμική εκπαίδευση: μια ερευνητική εφαρμογή σε Ρομά μαθητές Δημοτικού Σχολείου για την προσέγγιση της έννοιας «εκπαίδευση»
Authors: Παναγιωτακοπούλου Αρχοντία-Μυρτώ , Νικολάου Γεώργιος
Published: September 2024

Σκοπός της παρούσας μελέτης είναι να διερευνηθεί αν η εφαρμογή της μεθόδου της «Μετασχηματίζουσας Μάθησης μέσα από την Αισθητική Εμπειρία» στους 20 μαθητές ΡομάΓ΄, Δ΄ και Ε΄  Τάξης που φοιτούν στο 13οΔημοτικό Σχολεία είναι τελέσφορη, έτσι ώστε οιεκείνοι να κατανοήσουν τα οφέλη της συμμετοχής τους στην εκπαιδευτική διαδικασία. Για τον παραπάνω σκοπό ακολουθήσαμε και εστιάσαμε στα βήματα της μεθόδου της μετασχηματίζουσας μάθησης μέσα από την αισθητική εμπειρία. Επιπλέον χρησιμοποιήθηκε η μέθοδος της τριγωνοποίησης (triangulation) για την αναλυτική και επισταμένη διερεύνηση των ερευνητικών ερωτημάτων. Η έρευνά μας απέδειξε πως είναι αναγκαία η εφαρμογή εναλλακτικών και καινοτόμων πρακτικών όπως αυτή της μεθόδου της «Μετασχηματίζουσας Μάθησης μέσα από την Αισθητική Εμπειρία» προκειμένου οι συγκεκριμένοι μαθητές Ρομά της Πρωτοβάθμιας εκπαίδευσης να κατανοήσουν τα οφέλη της συμμετοχής τους στην εκπαιδευτική διαδικασία.