bluuebunny/crossref_metadata_2025 huggingface dataset:
The User-Centered Design of a Clinical Dashboard and Patient-Facing App for Gestational Diabetes
Authors: Kirkwood Jasmine R. , Dickson Jane , Stevens Marryat , Manataki Areti , Lindsay Robert S. , Wake Deborah J. , Reynolds Rebecca M.
Published: November 2024

Background:

The number of pregnancies affected by gestational diabetes mellitus (GDM) is growing. With the increased use of smartphones and predictive modeling, a mobile health (mHealth) solution could be developed to improve care and management of GDM while streamlining care through risk stratification.

Methods:

A user-centered mHealth tool was designed from ethnographic observations and 11 semi-structured interviews (six health care professionals [HCPs] and five women with GDM), followed by iterative changes and evaluation from three feedback groups with 31 participants (17 HCPs, 14 researchers) and 13 questionnaires with women with GDM.

Results:

“MyGDM” includes a clinical dashboard that centralizes the clinic’s patients, highlighting off-target blood glucose and predicting the need for pharmacological intervention. It is linked with a patient-facing app that includes structured education, culturally inclusive language options, and meal ideas. Through the feedback sessions, iterative changes were made around visualization and patient safety, and participants were positive toward the potential user experience. In the 13 questionnaires with women with GDM, 100% said it would fit into their lifestyle and help them manage GDM. Educational resources and the “request a call” functions were well received with 61.5% (8/13) and 69.2% (9/13) saying they were very likely or likely to use these, respectively.

Conclusion:

A user-centered mHealth tool consisting of a clinical dashboard linked with a patient-facing app for GDM care and management has been designed. Evaluation of the interactive design by end users was positive and showed that it met their needs.
Oral ibuprofen versus placebo in closure of patent ductus arteriosus in preterm neonates, a randomized control trial
Authors: El Sherif Dalia Fathi , El Raggal Nehal Mohamed , Nasef Marwa Waheed , Saleh Ghada Ahmad , Youssef Nada Hussein , Metwally Mohamed Hussein
Published: November 2024

Background

A consensus on treatment of patent ductus arteriosus (PDA) in preterm neonates remains elusive. Conservative management has recently gained popularity due to medical treatment lacking the evidence of benefit in terms of mortality and morbidity.

Objective

This study compares the efficacy of the standard dose of oral Ibuprofen versus placebo in the closure of PDA in preterm neonates ≤34 weeks gestation.

Methods

Eighty enrolled preterm neonates with a hemodynamically significant PDA (hsPDA) were randomized to either receive an early 3-day course oral ibuprofen or placebo (1:1). The open-label option and an extended oral ibuprofen therapy were offered if there were concerns over patient’s clinical condition being attributed to PDA and only if showing evidence of systemic and/or pulmonary hyperperfusion.

Results

No significant difference in PDA closure between both groups (62.5% vs 65% in Ibuprofen & placebo group respectively, p = .816). No significant difference was observed between groups in mortality ( p = 1), Bronchopulmonary dysplasia (BPD) ( p = 1), or necrotizing enterocolitis (NEC) (0.5). Placebo group required a longer duration of inotropic support (median of 10 vs 7.5 days in Ibuprofen group, p = .013) and were prescribed more diuretic therapy (27 vs 18 in Ibuprofen group, p = .043).

Conclusion

The standard dose of oral ibuprofen was comparable to placebo in early treatment of hsPDA in preterm neonates less than 34 weeks in terms of effect on ductal closure after one course of treatment, incidence of mortality, and morbidities like NEC, and BPD. Failure of ductal closure itself was associated in both groups with increased mortality, failure to reach full feeds, and more use of vasopressors and inotropes.
Serial VerifyNow P2Y12 platelet reactivity units in cerebral aneurysm patients treated with ticagrelor surrounding stent-coiling or flow diversion
Authors: Bielinski Tyler M. , Koul Prateeka , Collins Malie K. , Goren Oded , Weiner Gregory M. , Griessenauer Christoph J. , Schirmer Clemens M. , Hendrix Philipp
Published: November 2024

Introduction

Platelet function testing using serial VerifyNow P2Y12 platelet reactivity units (PRUs) is established for guiding clopidogrel antiplatelet therapy in cerebral aneurysm stenting procedures. However, for ticagrelor, the impact of serial PRU testing and the identification of safe PRU ranges remains unexplored.

Methods

Flow diversion stenting ( n = 232) and stent-assisted coiling procedures ( n = 83) performed 05/2017–12/2021 were reviewed. Out of these, 31 flow diversion and 18 stent-coiling procedures were performed on 44 patients using ticagrelor. Baseline demographics, ticagrelor PRUs, and clinical outcomes were assessed.

Results

Collectively, 257 ticagrelor P2Y12 PRUs were obtained. PRUs were <100 in 192/257 (74.7%) tests. Only 11/257 (4.3%) PRUs were >200. The overall median ticagrelor PRU was 38 (IQR 11–101). Among the 49 procedures, median PRUs before the procedure (25, IQR 10–67), on the day of the procedure (68, IQR 44–117), and on the day after the procedure (37, IQR 21–79) did not show the significant differences between the groups. A total of seven thromboembolic complications occurred. Median PRUs surrounding the thromboembolic complications (median 182, IQR 148–235) were significantly higher than preprocedural ( p < .001), day of surgery ( p < .01), and postprocedural PRUs ( p < .01). All seven procedures harbored demographic, anatomic, or procedural features increasing the risk for thromboembolic complications.

Discussion

The majority of periprocedural ticagrelor PRUs were <100. PRUs at the time point of thromboembolic complications were >120. Despite procedure-complicating features in each thromboembolic case, it raises the question whether safe ticagrelor PRU levels might be lower than those commonly applied for clopidogrel.
Start With a Joke: Humor, Presenter’s Status, Gender, and Investment Level
Authors: Reizer Abira , Brender-Ilan Yael
Published: November 2024

While previous work suggested that presenters may benefit from the use of humor, others argue that the use of humor can be risky. Therefore, there is a need to examine the potential moderators and mediators of this process. The study aims to experimentally explore the appropriate use of humor during a professional investment presentation. The sample included 400 participants. After being randomly assigned to 2 × 2 between-subjects conditions (man /woman presenter × with/without a humorous message), the participants watched a video of an investment presentation. Participants who were asked to invest virtual money in the firm after the video. Using a moderated mediation analysis, the results show that humor was related to higher investment amounts and that the presenters’ perceived organizational status mediated this indirect relationship. The novelty of the study lies in its experimental design, focusing on audience behavioral tendencies and its unexplored mixed-gender effect: women tended to invest less when a male presenter used humor, while men tended to invest more when a female presenter used humor. The perceived status of the presenter mediated these associations. Theoretically, the study expands the understanding of the Benign Violation Theory (BVT) regarding the need to address contextual factors while examining the appropriate use of humor. Moreover, to maximize the benefits of humor, one must consider the humor’s relevance to the audience and acknowledge that humor needs to be appropriately used. This is particularly important for people working in investment settings.
An ontological transition in higher education: Space, power and technology
Authors: Marginson Simon
Published: November 2024

The paper provides an overview of geopolitical developments and tensions in universities and science, and the impact in social space-making and relations of power. Innovations in space-making in higher education combine pre-given materiality with the ideas and interpretations of agents, and the social practices they develop, some of which become part of the ongoing materiality of the sector. One example of global space-making is the Academic Ranking of World Universities (the ‘Shanghai Ranking’), an early example of China ‘going out’ in higher education to transform global university relations. Global evolution in universities and science has passed through three historical layers, all of which enter into current practice: 1) the beginnings of post-coloniality and the 1945 UN Charter and its sovereign international order; (2) from 1990 onwards the strengthening of neo-coloniality in Pax Americana and U.S.-led processes of accelerated globalization; (3) in the last 15 years the partial fragmentation of the neo-colonial order amid growing multi-polarity and the rise of China. The paper expands on present issues and tensions, including the advent of AI in education and research (which should be the subject of international cooperation but is not), and the U.S.-driven closure of relations with China in science and technology. It argues that the decoupling strategy is ill-conceived, and while it has been disruptive it is unlikely to achieve its goals. Despite the geopolitics universities need to find ways of nurturing and developing a cooperative global space based on mutual respect.
Film review: The Archies, Producers: Jon Goldwater, Sharad Devarajan, Reema Kagti, Zoya Akhtar, Director: Zoya Akhtar
Authors: Tuli Nivedita , Borah Anasuya Swapna
Published: November 2024

The Archies, Producers: Jon Goldwater, Sharad Devarajan, Reema Kagti, Zoya Akhtar, Director: Zoya Akhtar, Hindi, 144 minutes, 2023.
Translatability of Craniofacial Devices into Low-Middle Income Countries: A Systematic Review
Authors: Chaij Jasmine M. , Tin Giovanni , Nguyen Khoa N. , French Brooke , Khechoyan David , Runyan Christopher M. , Nguyen Phuong D.
Published: November 2024

Introduction/Purpose: Globally, craniofacial surgery is limited due to disparities in expertise and resources. Lack of treatment results in a negative impact on function, development, and social stigma, increasing the burden of disability-adjusted life years in low- and middle-income countries (LMIC). A systematic review was performed to evaluate craniofacial surgeries requiring craniofacial devices and their translation into LMICs. Materials/Methods: A systematic review via PRISMA guidelines was conducted with keywords for distraction terms OR craniofacial devices terms AND low/middle-income country terms OR reuse/cost/accessibility terms. These terms were applied to databases OVID (Medline), Cumulated Index to Nursing and Allied Health Literature (CINAHL), and Scopus and the register, Cochrane Trials. Records were further screened by abstract by 3 reviewers for inclusion. Results: Two hundred and nineteen articles were identified after screening by abstract. Twenty-six articles met the inclusion criteria. LMICs represented included India, Niger, Nigeria, Vietnam, and Syria. Non-LMICs that provided solutions to increasing access for LMICs included Brazil, Chile, Japan, Mexico, Poland, the Netherlands, South Africa, and Turkey. Costs, resources, the need for multiple surgical interventions or devices, and a lack of surgical expertise were listed as barriers to care. Proposed solutions included capacity building via high-income country (HIC) involvement, 3D modeling and printing, reusing devices, new device implementation, and modification of existing devices. Conclusion: Innovation is needed to overcome healthcare barriers in LMICs. With partnership, support, and resourcefulness, craniofacial surgery can be developed safely in LMICs.
The techniques, efficacy and safety of penile glans augmentation using hyaluronic acid for the treatment of premature ejaculation: a systematic review and meta-analysis
Authors: Mohd Hashim Mohammad Hifzi , Md Zainuddin Zulkifli , Fam Xeng Inn , Khoo Hau Chun , Azizi Muhammad Hasif , Shukor Suzliza , Chin Kok-Yong , Iqbal Hussain Rizuana , Lim Li Yi
Published: November 2024

Background

Premature ejaculation (PE) is the most common self-reported sexual disorder among men, affecting up to 20% of the population. Recently, the injection of hyaluronic acid (HA) as a bulking agent into the glans of the penis was proposed as a promising modality for PE. It is believed to act as a barrier between the skin and nerve terminals, leading to decreased sensation of the glans penis, indirectly improving the outcome of PE. This scoping review aims to provide an overview of the techniques, efficacy, and safety of the injection of HA for PE derived from the existing scientific literature.

Main body

A literature search was conducted using PubMed, Scopus, and Web of Science databases and the keywords “hyaluronic acid” and “premature ejaculation.” Original articles were selected for further evaluation, while both case reports and case series were excluded. After the screening, ten relevant studies were included, with two main methods of injection, the Fanning technique and multiple puncture techniques, which were applied in the previous studies. All studies showed compelling improvements in both the intravaginal ejaculation latency time (IELT) and patients’ satisfaction. IELT increments may reach up to 8.54-fold even in the first month and sustain significantly up to 12 months. The complications reported, such as bleeding, pain, swelling, and discoloration, were mild and self-limited, which then resolved between 2 weeks and 1 month. No serious adverse events were reported.

Conclusions

With adequate surgical training and proper patient selection, penile augmentation using hyaluronic acid is a safe and effective method in the management of premature ejaculation.
Evolution of minimally invasive cholecystectomy: a narrative review
Authors: Nam Changjin , Lee Jun Suh , Kim Ji Su , Lee Tae Yoon , Yoon Young Chul
Published: November 2024

Background

Laparoscopic cholecystectomy, being a prevalent abdominal surgical procedure, has transitioned through various innovative stages aimed at reducing the procedure's invasiveness. These stages encompass Single-Incision Laparoscopic Cholecystectomy (SILC), Mini Laparoscopic Cholecystectomy (MLC), Natural Orifice Transluminal Endoscopic Surgery (NOTES), and Robotic-Assisted Laparoscopic Cholecystectomy (RALC). The purpose of this review is to trace the evolution of minimally invasive cholecystectomy techniques, assess their status, and identify emerging trends and challenges in the field.

Method

An extensive review was performed to explore the evolution and characteristics of SILC, MLC, NOTES, and RALC. The approach involved an in-depth examination of literature available on PubMed, coupled with a critical assessment of surgical outcomes, associated complications, and technical hurdles posed by these methods.

Results

SILC, despite its potential for reduced scarring, exhibits an elevated risk of bile duct damage and incisional hernia occurrences. MLC, mirroring the standard technique closely, presents minor benefits without amplifying postoperative complications, hence, positing itself as a feasible choice for routine elective cholecystectomy. NOTES, although still facing technical challenges, the hybrid transvaginal procedure is gaining clinical interest. RALC, heralded for its augmented precision and dexterity, emerges as a potential future avenue, although necessitating further exploration to ascertain its efficacy and safety.

Conclusion

The progression of laparoscopic cholecystectomy methodologies embodies the surgical society's aspiration to minimize invasiveness whilst enhancing patient outcomes. This review endeavors to offer a structured discourse on SILC, MLC, NOTES, and RALC, aspiring to aid the ongoing deliberation on the judicious selection of surgical techniques in clinical practice.
Fostering links, building trust, and facilitating change: connectivity helps sustain longitudinal integrated clerkships in small rural and remote communities
Authors: Carrigan Brendan , MacAskill William , Pinidiyapathirage Janani , Walters Sherrilyn , Fuller Lara , Brumpton Kay
Published: November 2024

Background

Maldistribution of medical professionals presents a significant challenge globally and leads to inequitable healthcare access, particularly in remote areas. Longitudinal integrated clerkships (LICs) in rural areas can improve workforce distribution and may be an innovative contributor to solving maldistribution issues. However, to align with healthcare needs, LICs must be sustainable in small communities, which often have a limited medical workforce. This study investigates the key elements underpinning LIC sustainability in small communities.

Methods

This study adopted a constructivist research paradigm in which participants’ constructions of their experiences supporting LICs in small rural communities were explored. Participants were conveniently sampled from the LIC community of practice attending the 2021 virtual annual conference of the Consortium of Longitudinal Integrated Clerkships. Data were collected through video recording and thematically analysed to identify barriers and enablers to running sustainable LIC programmes.

Results

Eleven participants fulfilling key roles within LICs, including clinical school directors, program coordinators, and clinical educators, were recruited for the study. Thematic analysis indicated that it is Connectivity, expressed through three subthemes, Fostering Links, Building Trust, and Facilitating Change, which underpins sustainable LICs in small communities.

Conclusions

Connectivity is a strong mediator for sustainability of LICs and may be the central defining theme of LICs. Increasing connectivity through prioritizing community engagement, trust-building, and strategic investment enhances the sustainability of rural LICs, ensuring their continued positive contribution to medical workforce distribution in underserved areas.
The use and impact of surveillance-based technology initiatives in inpatient and acute mental health settings: a systematic review
Authors: Griffiths Jessica L. , Saunders Katherine R. K. , Foye Una , Greenburgh Anna , Regan Ciara , Cooper Ruth E. , Powell Rose , Thomas Ellen , Brennan Geoff , Rojas-García Antonio , Lloyd-Evans Brynmor , Johnson Sonia , Simpson Alan
Published: November 2024

Background

The use of surveillance technologies is becoming increasingly common in inpatient mental health settings, commonly justified as efforts to improve safety and cost-effectiveness. However, their use has been questioned in light of limited research conducted and the sensitivities, ethical concerns and potential harms of surveillance. This systematic review aims to (1) map how surveillance technologies have been employed in inpatient mental health settings, (2) explore how they are experienced by patients, staff and carers and (3) examine evidence regarding their impact.

Methods

We searched five academic databases (Embase, MEDLINE, PsycInfo, PubMed and Scopus), one grey literature database (HMIC) and two pre-print servers (medRxiv and PsyArXiv) to identify relevant papers published up to 19/09/2024. We also conducted backwards and forwards citation tracking and contacted experts to identify relevant literature. The Mixed Methods Appraisal Tool assessed quality. Data were synthesised narratively.

Results

Thirty-two studies met the inclusion criteria. They reported on CCTV/video monitoring (n = 13), Vision-Based Patient Monitoring and Management (n = 9), body-worn cameras (n = 6), GPS electronic monitoring (n = 2) and wearable sensors (n = 2). Sixteen papers (50.0%) were low quality, five (15.6%) medium quality and eleven (34.4%) high quality. Nine studies (28.1%) declared a conflict of interest. Qualitative findings indicate patient, staff and carer views of surveillance technologies are mixed and complex. Quantitative findings regarding the impact of surveillance on outcomes such as self-harm, violence, aggression, care quality and cost-effectiveness were inconsistent or weak.

Conclusions

There is currently insufficient evidence to suggest that surveillance technologies in inpatient mental health settings are achieving their intended outcomes, such as improving safety and reducing costs. The studies were generally of low methodological quality, lacked lived experience involvement, and a substantial proportion (28.1%) declared conflicts of interest. Further independent coproduced research is needed to more comprehensively evaluate the impact of surveillance technologies in inpatient settings. If they are to be implemented, all key stakeholders should be engaged in the development of policies, procedures and best practice guidance to regulate their use, prioritising patients’ perspectives.
ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3
Authors: Lin Isabella , Awamleh Zain , Sinvhal Mili , Wan Andrew , Bondhus Leroy , Wei Angela , Russell Bianca E. , Weksberg Rosanna , Arboleda Valerie A.
Published: November 2024

Background

Rare variants in epigenes (a.k.a. chromatin modifiers), a class of genes that control epigenetic regulation, are commonly identified in both pediatric neurodevelopmental syndromes and as somatic variants in cancer. However, little is known about the extent of the shared disruption of signaling pathways by the same epigene across different diseases. To address this, we study an epigene, Additional Sex Combs-like 1 (ASXL1), where truncating heterozygous variants cause Bohring-Opitz syndrome (BOS, OMIM #605039), a germline neurodevelopmental disorder, while somatic variants are driver events in acute myeloid leukemia (AML). No BOS patients have been reported to have AML.

Methods

This study explores common pathways dysregulated by ASXL1 variants in patients with BOS and AML. We analyzed whole blood transcriptomic and DNA methylation data from patients with BOS and AML with ASXL1-variant (AML-ASXL1) and examined differential exon usage and cell proportions.

Results

Our analyses identified common molecular signatures between BOS and AML-ASXL1 and highlighted key biomarkers, including VANGL2, GRIK5 and GREM2, that are dysregulated across samples with ASXL1 variants, regardless of disease type. Notably, our data revealed significant de-repression of posterior homeobox A (HOXA) genes and upregulation of Wnt-signaling and hematopoietic regulator HOXB4. While we discovered many shared epigenetic and transcriptomic features, we also identified differential splice isoforms in RUNX3 where the long isoform, p46, is preferentially expressed in BOS, while the shorter p44 isoform is expressed in AML-ASXL1.

Conclusion

Our findings highlight the strong effects of ASXL1 variants that supersede cell-type and even disease states. This is the first direct comparison of transcriptomic and methylation profiles driven by pathogenic variants in a chromatin modifier gene in distinct diseases. Similar to RASopathies, in which pathogenic variants in many genes lead to overlapping phenotypes that can be treated by inhibiting a common pathway, our data identifies common pathways for ASXL1 variants that can be targeted for both disease states. Comparative approaches of high-penetrance genetic variants across cell types and disease states can identify targetable pathways to treat multiple diseases. Finally, our work highlights the connections of epigenes, such as ASXL1, to an underlying stem-cell state in both early development and in malignancy.
Associations of perceived neighbourhood and home environments with sedentary behaviour among adolescents in 14 countries: the IPEN adolescent cross sectional observational study
Authors: Anjana Ranjit Mohan , Ranjani Harish , Cerin Ester , Akram Muhammad , Salmon Jo , Conway Terry L. , Cain Kelli L. , Pradeepa Rajendra , Barnett Anthony , Sit Cindy H. P. , Van Dyck Delfien , Hino Adriano Akira , Pizarro Andreia , Oyeyemi Adewale L. , Muda Wan Abdul Manan Wan , Moran Mika R. , Troelsen Jens , Mitáš Josef , Islam M. Zakiul , Queralt Ana , Mohan Viswanathan , Hinckson Erica , Sallis James F.
Published: November 2024

Background

Understanding environmental correlates of sedentary behaviour (SB) among young people is important as such data can identify approaches to limit sedentary time. This paper estimates associations of parent-reported neighbourhood and adolescent-reported home environments with SB among adolescents aged 11–19 years from 14 countries.

Methods

In the International Physical activity and the Environment Network (IPEN) Adolescent Study (an observational, cross-sectional multi-country study), adolescents wore a triaxial accelerometer for seven days that assessed sedentary time (ST). Adolescents completed survey measures of sedentary behaviour (SB) related to recreational screen time and sitting time in motor vehicles. Parents and adolescents completed surveys assessing neighbourhood and home environments. Accelerometer based ST was available in 3,982 adolescents while survey data were available for 6,302 dyads. We estimated the total and direct effects of each environmental attribute on ST and SB. Sex of the adolescent and city/country were examined as moderators.

Results

The average ST in adolescents from 14 countries ranged from 7.8 to 10.5 h/day. Personal social media was the only significant correlate of total ST across both sexes. With respect to self-reported SB, adolescents accumulated an average of 3.8 h of non-school screen time per day and nearly 40 min of transport-related sitting time. Screen time was associated with all home environment variables, including social media account, as well as land use mix—diversity, traffic safety, and crime safety. Transport-related sitting time was related to land use mix—diversity, recreation facilities, walking facilities, and pedestrian infrastructure, but no home environment variables. City/country and sex were significant moderators of several associations.

Conclusions

Both home and neighbourhood environment features were related to ST and SB. Having social media accounts emerged as a major contributor towards sedentarism in adolescents.
Towards a risk assessment framework for micro- and nanoplastic particles for human health
Authors: Vogel Amelie , Tentschert Jutta , Pieters Raymond , Bennet Francesca , Dirven Hubert , van den Berg Annemijne , Lenssen Esther , Rietdijk Maartje , Broßell Dirk , Haase Andrea
Published: November 2024

Background

Human exposure to micro- and nanoplastic particles (MNPs) is inevitable but human health risk assessment remains challenging for several reasons. MNPs are complex mixtures of particles derived from different polymer types, which may contain plenty of additives and/or contaminants. MNPs cover broad size distributions and often have irregular shapes and morphologies. Moreover, several of their properties change over time due to aging/ weathering. Case-by-case assessment of each MNP type does not seem feasible, more straightforward methodologies are needed. However, conceptual approaches for human health risk assessment are rare, reliable methods for exposure and hazard assessment are largely missing, and meaningful data is scarce.

Methods

Here we reviewed the state-of-the-art concerning risk assessment of chemicals with a specific focus on polymers as well as on (nano-)particles and fibres. For this purpose, we broadly screened relevant knowledge including guidance documents, standards, scientific publications, publicly available reports. We identified several suitable concepts such as: (i) polymers of low concern (PLC), (ii) poorly soluble low toxicity particles (PSLT) and (iii) fibre pathogenicity paradigm (FPP). We also aimed to identify promising methods, which may serve as a reasonable starting point for a test strategy.

Results and conclusion

Here, we propose a state-of-the-art modular risk assessment framework for MNPs, focusing primarily on inhalation as a key exposure route for humans that combines several integrated approaches to testing and assessment (IATAs). The framework starts with basic physicochemical characterisation (step 1), followed by assessing the potential for inhalative exposure (step 2) and includes several modules for toxicological assessment (step 3). We provide guidance on how to apply the framework and suggest suitable methods for characterization of physicochemical properties, exposure and hazard assessment. We put special emphasis on new approach methodologies (NAMs) and included grouping, where adequate. The framework has been improved in several iterative cycles by taking into account expert feedback and is currently being tested in several case studies. Overall, it can be regarded as an important step forward to tackle human health risk assessment.
Shifting focus from ideality to reality: a qualitative study on how quality of life is defined by premanifest and manifest Huntington’s disease gene expansion carriers
Authors: van Lonkhuizen Pearl J. C. , Heemskerk Anne-Wil , Slutter Leanne , van Duijn Erik , de Bot Susanne T. , Chavannes Niels H. , Meijer Eline ,   on behalf of the HEALTHE-RND consortium, Vegt Niko , Chavannes Niels , Heemskerk Anne- Wil , de Bot Susanne T. , van Lonkhuizen Pearl J. C. , Vegt Niko , Feleus Stephanie , Arendts Esther C , Putman Amy , Landwehrmeyer G. Bernhard , Mühlbäck Alzbeta , Frank Wiebke , Steck Franziska , Klempíř Jiří , Konvalinková Romama , Bezuchová Eva , Dolečková Kristýna , Klempířová Olga , Roth Jan , Ulmanová Olga , Squitieri Ferdinando , Maffi Sabrina , Scaricamazza Eugenia , Migliore Simone , Giorgio Chiara , D’Alessio Barbara , Casella Melissa , Hoblyn Jennifer , Thangaramanujam Muthukumaran , Burke Tom , O’Malley Emer , McKenna Stephen , McKenna Ian , Thorpe Jeanette , Coffey Anna , Moldovan Ramona , Foley Peter , Kerr Jacqueline
Published: November 2024

Background

Understanding quality of life (QoL) is important in diseases for which there is no cure to date, such as Huntington’s disease (HD). A deeper level of understanding is, however, compromised by the lack of studies examining QoL from the perspectives of HD gene expansion carriers (HDGECs). Only a few qualitative studies on QoL in HD have been performed, yet none investigated how QoL is defined by HDGECs themselves.

Objective

This qualitative study explores how premanifest and manifest HDGECs define their QoL.

Methods

Online semi-structured interviews were conducted with 6 premanifest and 6 manifest HDGECs in the Netherlands. Qualitative content analysis was used to explore participants’ QoL definitions via inductive coding and the subsequent formulation of (sub)categories and (sub)themes.

Results

Premanifest and manifest HDGECs had a different focus when defining QoL. Two subthemes were identified for premanifest HDGECs: Thoughts about a meaningful life regardless of HD and Concerns about the future progression and impact of HD. For manifest HDGECs, two other subthemes were identified: Coming to terms with HD and Shifting perspectives due to the impact of HD. One overall theme was generated, reflecting the difference and adaptive shift in focus between premanifest and manifest HDGECs: Shifting focus from ideality to reality.

Conclusions

In providing optimal care, HDGECs should be considered as part of a complex, continuously changing environment, thereby taking into account their individual QoL experiences and tailoring care accordingly. HDGECs might benefit from forming helpful beliefs about future adaptability and resilience and developing adaptive coping strategies.
Seeding activity of skin misfolded tau as a biomarker for tauopathies
Authors: Wang Zerui , Wu Ling , Gerasimenko Maria , Gilliland Tricia , Shah Zahid Syed Ali , Lomax Evalynn , Yang Yirong , Gunzler Steven A. , Donadio Vincenzo , Liguori Rocco , Xu Bin , Zou Wen-Quan
Published: November 2024

Background

Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically hyperphosphorylated tau protein in the brain, leading to prion-like aggregation and propagation. They include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Currently, reliable diagnostic biomarkers that directly reflect the capability of propagation and spreading of misfolded tau aggregates in peripheral tissues and body fluids are lacking.

Methods

We utilized the seed-amplification assay (SAA) employing ultrasensitive real-time quaking-induced conversion (RT-QuIC) to assess the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies, including AD, PSP, CBD, and PiD, compared to normal controls.

Results

We found that the skin tau-SAA demonstrated a significantly higher sensitivity (75–80%) and specificity (95–100%) for detecting tauopathy, depending on the tau substrates used. Moreover, the increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients examined. Analysis of the end products of skin-tau SAA confirmed that the increased seeding activity was accompanied by the formation of tau aggregates with different physicochemical properties related to two different tau substrates used.

Conclusions

Overall, our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of misfolded tau in the skin could serve as a diagnostic biomarker for tauopathies.
Lung ultrasound for the diagnosis of subpleural consolidations - a review of the veterinary and human literature
Authors: Gajewski Michał
Published: November 2024

Lung ultrasound (LUS) is an imaging modality of growing importance in human medicine. LUS has been extensively applied to human patients. Guidelines have been created for internal medicine, describing ultrasonographic features of various lung pathologic processes. Such guidelines do not exist for veterinary medicine, and studies on the utility of LUS in companion animals are limited. Therefore, this review compares conclusions from veterinary studies to recommendations in human medicine for the detection of subpleural consolidations beyond the application of LUS as a point-of-care modality in emergency and critical care.
Chemogenetic silencing of the subiculum blocks acute chronic temporal lobe epilepsy
Authors: Lin Jianbang , Liu Jing , Zhang Qi , Liu Taian , Hong Zexuan , Lu Yi , Zhong Cheng , Lu Zhonghua , Li Yuantao , Hu Yu
Published: November 2024

Temporal lobe epilepsy (TLE) is the most common form of medically-intractable epilepsy. Subicular hyperexcitability is frequently observed with TLE, presumably caused by impaired inhibition of local excitatory neurons. Here, we evaluated the effectiveness of silencing subicular pyramidal neurons to treat a rodent model of TLE. First, we generated a chronic TLE mouse model via initial intrahippocampal kainic acid (IHKA) injection. In the chronic state after first IHKA injection, behavioral seizures and histological abnormalities were reliably observed. We then injected an adeno-associated viral (AAV) vector carrying an inhibitory chemogenetic element, hM4Di, directly into the subiculum. Eight weeks after the first IHKA injection, acute seizures were induced by giving a second dose of kainic acid (KA), which mimicked generalized tonic–clonic seizures. Herein, precise control over generalized tonic–clonic seizure onset was achieved via this two-step process. We found that chemogenetic suppression of subicular pyramidal neurons had a robust anti-epileptogenesis effect in this acute-chronic model of TLE. These data confirm a crucial role of the subiculum in the propagation of hippocampal seizures and highlight the potential for using subicular chemogenetic manipulation to treat generalized tonic–clonic seizures.
AKT kinases as therapeutic targets
Authors: Hassan Dalal , Menges Craig W. , Testa Joseph R. , Bellacosa Alfonso
Published: November 2024

AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While some have recently garnered attention for their favorable profile, concern over resistance and off-target effects have continued to hinder their widespread adoption in the clinic, mandating a discussion on alternative modes of targeting. In this review, we discuss isoform-centric targeting that may be more effective and less toxic than traditional pan-AKT inhibitors and its significance for disease prevention and treatment, including immunotherapy. We also touch on the emerging mutant- or allele-selective covalent allosteric AKT inhibitors (CAAIs), as well as indirect, novel AKT-targeting approaches, and end with a briefing on the ongoing quest for more reliable biomarkers predicting sensitivity and response to AKT inhibitors, and their current state of affairs.
Decoding the synergy: unveiling gradient boosting regression model for multivariate quantitation of pioglitazone, alogliptin and glimepiride in pure and tablet dosage forms
Authors: Elkhoudary Mahmoud M. , Marie Aya A. , Hammad Sherin F. , Salim Mohamed M. , Kamal Amira H.
Published: November 2024

This study represents a comparison among the performances of four multivariate procedures: partial least square (PLS) and artificial neural networks (ANN) in addition to support vector regression (SVR) and extreme gradient boosting (XG Boost) algorithm for the determination of the anti-diabetic mixture of pioglitazone (PIO), alogliptin (ALG) and glimepiride (GLM) in pharmaceutical formulations with aid of UV spectrometry. Key wavelengths were selected using knowledge-based variable selection and various preprocessing methods (e.g., mean centering, orthogonal scatter correction, and principal component analysis) to minimize noise and improve model precision. XG Boost effectively enhanced computing speed and accuracy by focusing on specific spectral features rather than the entire spectrum, demonstrating its advantages in resolving complex, overlapping spectral data. The independent test results of different models demonstrated that XG Boost outperformed other methods. XG Boost achieved the lowest root mean squared error of prediction (RMSEP) and standard deviation (SD) values across all compounds, indicating minimal prediction error and variability. For PIO, XG Boost recorded an RMSEP of 0.100 and SD of 0.369, significantly better than PLS and ANN. For ALG, XG Boost showed near-perfect performance with an RMSEP of 0.001 and SD of 0.005, outperforming SVR and PLS, which had higher error rates. In the case of GLM, XG Boost also excelled with an RMSEP of 0.001 and SD of 0.018, demonstrating superior precision compared to the much higher errors seen in PLS and ANN. These results highlight XG Boost’s exceptional ability to handle complex, overlapping spectral data, making it the most reliable and accurate model in this study.
Non-metastatic causes of multiple pulmonary nodules
Authors: Akçiçek Esra , Durhan Gamze , Düzgün Selin Ardalı , Kurtulan Olcay , Akpınar Meltem Gülsün , Demirkazık Figen , Arıyürek Orhan Macit
Published: November 2024

Various processes, including benign or malignant (mostly metastasis) processes, contribute to the occurrence of multiple pulmonary nodules. For differential diagnosis, metastasis must be excluded as an etiological factor in patients who have multiple pulmonary nodules with a known primary malignancy. However, differential diagnosis of multiple pulmonary nodules caused by benign diseases and malignant processes is challenging. Multiple pulmonary nodules resulting from metastasis may mimic those resulting from infections, inflammatory processes, and rare benign diseases. Some rare diseases, such as pulmonary sclerosing pneumocytoma and pulmonary epithelioid hemangioendothelioma, or common diseases with a rare presentation of multiple nodules must be considered in the differential diagnosis of metastasis. In addition to the clinical and laboratory findings, radiological features are crucial for differential diagnosis. The size, density, location, and border characteristics (well-defined or poorly defined) of pulmonary nodules, as well as their internal structure (solid, subsolid, or ground glass nodule), growth rate during follow-up, and associated pulmonary and extrapulmonary findings are important for differential diagnosis along with clinical and laboratory data. This article summarizes the general features and imaging findings of these diseases, which less frequently present with multiple pulmonary nodules, and the clues that can be used to distinguish these diseases from metastasis.

Critical relevance statement

The radiological features, clinical findings, and temporal changes during follow-up are important in distinguishing non-metastatic causes of multiple pulmonary nodules from metastatic causes and guiding diagnosis and early treatment, especially in patients with primary malignancy.

Key Points

Multiple pulmonary nodules have a wide range of etiologies, including metastatic disease.

Metastasis as an etiology must be excluded in patients with multiple pulmonary nodules.

Correlation of radiological findings (nodule size, position, and associated findings) with clinical history is crucial for differential diagnosis.

Graphical Abstract
Identification of neural alterations in patients with Crohn’s disease with a novel multiparametric brain MRI-based radiomics model
Authors: Zhang Ruo-nan , Wang Yang-di , Wang Hai-jie , Ke Yao-qi , Shen Xiao-di , Huang Li , Lin Jin-jiang , He Wei-tao , Zhao Chen , Li Zhou-lei , Mao Ren , Wang Ye-jun , Yang Guang , Li Xue-hua
Published: November 2024

Objectives

Gut-brain axis dysfunction has emerged as a key contributor to the pathogenesis of Crohn’s disease (CD). The elucidation of neural alterations may provide novel insights into its management. We aimed to develop a multiparameter brain MRI-based radiomics model (RM) for characterizing neural alterations in CD patients and to interpret these alterations using multiomics traits.

Methods

This prospective study enrolled 230 CD patients and 46 healthy controls (HCs). Participants voluntarily underwent brain MRI and psychological assessment (n = 155), blood metabolomics analysis (n = 260), and/or fecal 16S rRNA sequencing (n = 182). The RM was developed using 13 features selected from 13,870 first-order features extracted from multiparameter brain MRI in training cohort (CD, n = 75; HCs, n = 32) and validated in test cohort (CD, n = 34; HCs, n = 14). Multiomics data (including gut microbiomics, blood metabolomics, and brain radiomics) were compared between CD patients and HCs.

Results

In the training cohort, area under the receiver operating characteristic curve (AUC) of RM for distinguishing CD patients from HCs was 0.991 (95% confidence interval (CI), 0.975–1.000). In test cohort, RM showed an AUC of 0.956 (95% CI, 0.881–1.000). CD-enriched blood metabolites such as triacylglycerol (TAG) exhibited significant correlations with both brain features detected by RM and CD-enriched microbiota (e.g., Veillonella). One notable correlation was found between Veillonella and Ctx-Lh-Middle-Temporal-CBF-p90 (r = 0.41). Mediation analysis further revealed that dysbiosis, such as of Veillonella, may regulate the blood flow in the middle temporal cortex through TAG.

Conclusion

We developed a multiparameter MRI-based RM that characterized the neural alterations of CD patients, and multiomics data offer potential evidence to support the validity of our model. Our study may offer clues to help provide potential therapeutic targets.

Critical relevance statement

Our brain-gut axis study developed a novel model using multiparameter MRI and radiomics to characterize brain changes in patients with Crohn’s disease. We validated this model’s effectiveness using multiomics data, making it a potential biomarker for better patient management.

Key Points

Utilizing multiparametric MRI and radiomics techniques could unveil Crohn’s disease’s neurophenotype.

The neurophenotype radiomics model is interpreted using multiomics data.

This model may serve as a novel biomarker for Crohn’s disease management.

Graphical Abstract
Modern contraceptive use among currently married non-pregnant women (aged 15–49 years) in West Bengal, India: a reflection from NFHS-5
Authors: Sen Susanta , Banerjee Amit , Ali Asif , Chakma Namita
Published: November 2024

Background

There is a dearth of research on modern family planning practices in high focus states like West Bengal in India with diverse population groups and distinct health needs. Thus, this study aims to investigate the latest picture of modern contraceptive use and its associated socio-demographic factors among currently married non-pregnant of reproductive aged (15–49 years) women in West Bengal.

Methods

The study is based on secondary data, collected from the fifth round of the National Family Health Survey (NFHS-5; 2019-20). A total of 15,841 currently married non-pregnant women were included into this study. With the overarching goal of understanding the determinants and patterns of modern contraceptive use, the study employed a combination of bi-variate and multivariate analyses, including logistic regression.

Results

The results reveal that female sterilization is the most common modern contraceptive method across the state. Contraceptive use varies by district, from 43% in Puruliya to 77.3% in Birbhum. Women aged 30–34 were significantly more likely to use contraception (OR = 1.47), while those aged 45–49 were less likely to use it (OR = 0.74). Women with mixed gender composition of living children (OR = 1.48) were more likely to use contraception, compared to women with no children (OR = 0.21) or daughters only (OR = 0.80). SC women (OR = 1.63) and Christians (OR = 2.17) showed higher usage. Wealthier women (OR = 1.26) and urban residents also reported higher use. Moreover, son preference continues and women married after 18 are less likely to adopt modern methods. These findings highlight the need to improve reproductive health outcomes and overcome barriers to increasing contraceptive uptake.

Conclusion

Targeted interventions focusing on education, awareness-building, and improving access to diverse contraceptive options are recommended to empower women in making informed reproductive choices and advancing reproductive rights and health equity. Also, effective modern contraceptive services must overcome legal policy, social, cultural and structural barriers to benefit more women.