bluuebunny/crossref_metadata_2025 huggingface dataset:
Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis
Authors: Wang Michael , Robak Tadeusz , Maddocks Kami J. , Phillips Tycel , Smith Stephen D. , Gallinson David , Calvo Roser , Wun Chuan-Chuan , Munugalavadla Veerendra , Jurczak Wojciech
Published: May 2024

This phase 1b study evaluated safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease (PD) or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until PD, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled; 95.2% completed induction (6 AVR cycles) and 47.6% continued acalabrutinib maintenance. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs and 5 [23.8%] deaths, all among unvaccinated patients). There was no grade ≥3 atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) was 100% (95% CI, 83.9-100.0) with 71.4% complete response. With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI, 67.0-97.5) and 63.2% (95% CI, 34.7-82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI, 70.7-99.3) and 75.2% (95% CI, 50.3-88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10–6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity. The trial was registered at www.ClinicalTrials.gov as #NCT02717624.
Bronchiectasis management in adults: state of the art and future directions
Authors: Choi Hayoung , McShane Pamela J. , Aliberti Stefano , Chalmers James D.
Published: May 2024

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials (RCTs) have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find “treatable traits” and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent RCTs.
Early serum biomarkers to characterise different phenotypes of primary graft dysfunction after lung transplantation: a systematic scoping review
Authors: Scaravilli Vittorio , Turconi Gloria , Colombo Sebastiano Maria , Guzzardella Amedeo , Bosone Marco , Zanella Alberto , Bos Lieuwe , Grasselli Giacomo
Published: May 2024

Background

Lung transplantation (LUTX) is often complicated by primary graft dysfunction (PGD). Plasma biomarkers hold potential for PGD phenotyping and targeted therapy. This scoping review aims to collect the available literature in search of serum biomarkers for PGD phenotyping.

Methods

Following JBI and PRISMA guidelines, we conducted a systematic review searching MEDLINE, Web of Science, EMBASE and The Cochrane Library for papers reporting the association between serum biomarkers measured within 72 h of reperfusion and PGD, following International Society for Heart and Lung Transplantation (ISHLT) guidelines. We extracted study details, patient demographics, PGD definition and timing, biomarker concentration, and their performance in identifying PGD cases.

Results

Among the 1050 papers screened, 25 prospective observational studies were included, with only nine conducted in the last decade. These papers included 1793 unique adult patients (1195 double LUTX, median study size 100 (IQR 44–119)). Most (n=21) compared PGD grade 3 to less severe PGD, but only four adhered to 2016 PGD definitions. Enzyme-linked immunosorbent assays and the multiplex bead array technique were utilised in 23 and two papers, respectively. In total, 26 candidate biomarkers were identified, comprising 13 inflammatory, three endothelial activation, three epithelial injury, three cellular damage and two coagulation dysregulation markers. Only five biomarkers (sRAGE, ICAM-1, PAI-1, SP-D, FSTL-1) underwent area under the receiver operating characteristic curve analysis, yielding a median value of 0.58 (0.51–0.78) in 406 patients (276 double LUTX).

Conclusions

Several biomarkers exhibit promise for future studies aimed at PGD phenotyping after LUTX. To uncover the significant existing knowledge gaps, further international prospective studies incorporating updated diagnostic criteria, modern platforms and advanced statistical approaches are essential.
Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit
Authors: Brown Jacquelyn A. , Faley Shannon L. , Judge Monika , Ward Patricia , Ihrie Rebecca A. , Carson Robert , Armstrong Laura , Sahin Mustafa , Wikswo John P. , Ess Kevin C. , Neely M. Diana
Published: May 2024

Background

Tuberous sclerosis complex (TSC) is a multi-system genetic disease that causes benign tumors in the brain and other vital organs. The most debilitating symptoms result from involvement of the central nervous system and lead to a multitude of severe symptoms including seizures, intellectual disability, autism, and behavioral problems. TSC is caused by heterozygous mutations of either the TSC1 or TSC2 gene and dysregulation of mTOR kinase with its multifaceted downstream signaling alterations is central to disease pathogenesis. Although the neurological sequelae of the disease are well established, little is known about how these mutations might affect cellular components and the function of the blood–brain barrier (BBB).

Methods

We generated TSC disease-specific cell models of the BBB by leveraging human induced pluripotent stem cell and microfluidic cell culture technologies.

Results

Using microphysiological systems, we demonstrate that a BBB generated from TSC2 heterozygous mutant cells shows increased permeability. This can be rescued by wild type astrocytes or by treatment with rapamycin, an mTOR kinase inhibitor.

Conclusion

Our results demonstrate the utility of microphysiological systems to study human neurological disorders and advance our knowledge of cell lineages contributing to TSC pathogenesis and informs future therapeutics.
Palliative care education: a nationwide qualitative study of emergency medicine residency program directors in the United Arab Emirates
Authors: Harhara Thana , Buhumaid Rasha , Oyoun Alsoud Leen , Ibrahim Halah
Published: May 2024

Background

Emergency medicine (EM) physicians routinely care for patients with serious life-limiting illnesses. Educating EM residents to have general skills and competencies in palliative medicine is a global priority. The purpose of this study was to describe the current status of palliative and end-of-life education in EM residency programs in the United Arab Emirates (UAE) and to identify barriers and opportunities to inculcating palliative care (PC) instruction into EM training in a non-Western setting.

Methods

Using the American College of Emergency Medicine’s milestones for Hospice and Palliative Medicine for Emergency Medicine as a question guide, semi-structured interviews were conducted with program directors of all 7 EM residency programs in the UAE from January through July 2023. Qualitative content analysis was conducted to identify recurring themes.

Results

All program directors agreed that PC knowledge and skills are essential components of training for EM residents but have had variable success in implementing a structured PC curriculum. Six themes emerged, namely the educational curriculum, PC policies and practices, comprehensive PC services, cultural and religious barriers to PC, EM scope of practice, and supporting residents after patient death.

Conclusion

UAE national EM residency curriculum development is evolving with an emphasis on developing a structured PC curriculum. As EM residencies implement policies and programs to improve care for patients and families dealing with serious illness, future studies are needed to assess the impact of these initiatives on patient quality of life and physician well-being.
DNA methylation analysis of floral parts revealed dynamic changes during the development of homostylous Fagopyrum tataricum and heterostylous F. esculentum flowers
Authors: Sala-Cholewa Katarzyna , Tomasiak Alicja , Nowak Katarzyna , Piński Artur , Betekhtin Alexander
Published: May 2024

Background

Proper flower development is essential for plant reproduction, a crucial aspect of the plant life cycle. This process involves precisely coordinating transcription factors, enzymes, and epigenetic modifications. DNA methylation, a ubiquitous and heritable epigenetic mechanism, is pivotal in regulating gene expression and shaping chromatin structure. Fagopyrum esculentum demonstrates anti-hypertensive, anti-diabetic, anti-inflammatory, cardio-protective, hepato-protective, and neuroprotective properties. However, the heteromorphic heterostyly observed in F. esculentum poses a significant challenge in breeding efforts. F. tataricum has better resistance to high altitudes and harsh weather conditions such as drought, frost, UV-B radiation damage, and pests. Moreover, F. tataricum contains significantly higher levels of rutin and other phenolics, more flavonoids, and a balanced amino acid profile compared to common buckwheat, being recognised as functional food, rendering it an excellent candidate for functional food applications.

Results

This study aimed to compare the DNA methylation profiles between the Pin and Thrum flower components of F. esculentum, with those of self-fertile species of F. tataricum, to understand the potential role of this epigenetic mechanism in Fagopyrum floral development. Notably, F. tataricum flowers are smaller than those of F. esculentum (Pin and Thrum morphs). The decline in DNA methylation levels in the developed open flower components, such as petals, stigmas and ovules, was consistent across both species, except for the ovule in the Thrum morph. Conversely, Pin and Tartary ovules exhibited a minor decrease in DNA methylation levels. The highest DNA methylation level was observed in Pin stigma from closed flowers, and the most significant decrease was in Pin stigma from open flowers. In opposition, the nectaries of open flowers exhibited higher levels of DNA methylation than those of closed flowers. The decrease in DNA methylation might correspond with the downregulation of genes encoding methyltransferases.

Conclusions

Reduced overall DNA methylation and the expression of genes associated with these epigenetic markers in fully opened flowers of both species may indicate that demethylation is necessary to activate the expression of genes involved in floral development.
Application of ultrasound-guided single femoral triangle and adductor canal block in arthroscopic knee surgery: a prospective, double-blind, randomized clinical study
Authors: Chen Baizhou , Tan Minghe , Li Qingshu , Wang Siqi , Chen Daiyu , Zhao Maoji , Cao Jun
Published: May 2024

Purpose

To compare the difference in analgesic effect between femoral triangle block (FTB) and adductor canal block (ACB) during arthroscopic knee surgery.

Methods

Patients who underwent arthroscopic knee surgery were randomized preoperatively to FTB group or ACB group. For each group, 20 mL of 0.1% ropivacaine was injected. Primary outcomes: The numeric rating score (NRS) at 12 h after surgery at rest and during movement. Secondary outcome: (1) The NRS at post anesthesia care unit (PACU) and 2, 24 h after surgery at rest and during movement; (2) The quadriceps muscle strength at PACU and 2, 12, 24 h after surgery; (3) Consumption of Rescue analgesia; (4) Incidence of adverse reactions.

Results

The NRS at 12 h after surgery at rest and during movement of ACB group were higher than FTB group. Among secondary outcomes, the NRS at PACU at rest and during movement, 2 h after surgery during movement of FTB group lower than ACB group; the quadriceps muscle strength at 2 h after surgery of FTB group stronger than ACB group. After multiple linear regression model analysis, the data showed additional statistically significant reduction NRS at 24 h after surgery at rest (0.757, p = 0.037) in FTB group. Other outcomes were similar between two groups.

Conclusions

The FTB appears to provide superior pain control after knee arthroscopy than ACB, the FTB is superior to the ACB in quadriceps muscle strength at 2 h after surgery.

Trial registration

The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300068765). Registration date: 28/02/2023.
Trends in dispensing errors reported in Finnish community pharmacies in 2015–2020: a national retrospective register-based study
Authors: Mäkinen Emilia , Holmström Anna-Riia , Airaksinen Marja , Schoultz Anna
Published: May 2024

Background

Community pharmacies are responsible for dispensing of medicines and related counselling in outpatient care. Dispensing practices have remarkably changed over time, but little is known about how the changes have influenced medication safety. This national study investigated trends in dispensing errors (DEs) related to prescribed medicines, which were reported in Finnish community pharmacies within a 6-year period.

Methods

This national retrospective register study included all DEs reported to a nationally coordinated voluntary DE reporting system by Finnish community pharmacies during 2015–2020. DE rates, DE types, prescription types, individuals who detected DEs and contributing factors to DEs were quantified as frequencies and percentages. Poisson regression was used to assess the statistical significance of the changes in annual DE rates by type.

Results

During the study period, altogether 19 550 DEs were reported, and the annual number of error reports showed a decreasing trend (n = 3 913 in 2015 vs. n = 2 117 in 2020, RR 0.54, p < 0.001). The greatest decrease in reported DEs occurred in 2019 after the national implementation of the Medicines Verification System (MVS) and the additional safety feature integrated into the MVS process. The most common error type was wrong dispensed strength (50% of all DEs), followed by wrong quantity or pack size (13%). The annual number of almost all DE types decreased, of which wrong strength errors decreased the most (n = 2121 in 2015 vs. n = 926 in 2020). Throughout the study period, DEs were most commonly detected by patients (50% of all DEs) and pharmacy personnel (30%). The most reported contributing factors were factors related to employees (36% of all DEs), similar packaging (26%) and similar names (21%) of medicinal products.

Conclusions

An overall decreasing trend was identified in the reported DEs and almost all DE types. These changes seem to be associated with digitalisation and new technologies implemented in the dispensing process in Finnish community pharmacies, particularly, the implementation of the MVS and the safety feature integrated into the MVS process. The role of patients and pharmacy personnel in detecting DEs has remained central regardless of changes in dispensing practices.
Understanding health service utilisation patterns for care home residents during the COVID-19 pandemic using routinely collected healthcare data
Authors: Garner Alex , Preston Nancy , Caiado Camila C S , Stubington Emma , Hanratty Barbara , Limb James , Mason Suzanne M , Knight Jo
Published: May 2024

Background

Healthcare in care homes during the COVID-19 pandemic required a balance, providing treatment while minimising exposure risk. Policy for how residents should receive care changed rapidly throughout the pandemic. A lack of accessible data on care home residents over this time meant policy decisions were difficult to make and verify. This study investigates common patterns of healthcare utilisation for care home residents in relation to COVID-19 testing events, and associations between utilisation patterns and resident characteristics.

Methods

Datasets from County Durham and Darlington NHS Foundation Trust including secondary care, community care and a care home telehealth app are linked by NHS number used to define daily healthcare utilisation sequences for care home residents. We derive four 10-day sets of sequences related to Pillar 1 COVID-19 testing; before [1] and after [2] a resident’s first positive test and before [3] and after [4] a resident’s first test. These sequences are clustered, grouping residents with similar healthcare patterns in each set. Association of individual characteristics (e.g. health conditions such as diabetes and dementia) with healthcare patterns are investigated.

Results

We demonstrate how routinely collected health data can be used to produce longitudinal descriptions of patient care. Clustered sequences [1,2,3,4] are produced for 3,471 care home residents tested between 01/03/2020–01/09/2021. Clusters characterised by higher levels of utilisation were significantly associated with higher prevalence of diabetes. Dementia is associated with higher levels of care after a testing event and appears to be correlated with a hospital discharge after a first test. Residents discharged from inpatient care within 10 days of their first test had the same mortality rate as those who stayed in hospital.

Conclusion

We provide longitudinal, resident-level data on care home resident healthcare during the COVID-19 pandemic. We find that vulnerable residents were associated with higher levels of healthcare usage despite the additional risks. Implications of findings are limited by the challenges of routinely collected data. However, this study demonstrates the potential for further research into healthcare pathways using linked, routinely collected datasets.
Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis
Authors: Satapathy Prakasini , Khatib Mahalaqua Nazli , Gaidhane Shilpa , Zahiruddin Quazi Syed , Serhan Hashem Abu , Sharma Rakesh Kumar , Sharma Divya , Arora Mithhil , Rustagi Sarvesh , NA AlKaabi , Alsayyah Ahmed , Al-Hajeili Marwan , Al-Subaie Maha F. , Alfaresi Mubarak , Alissa Mohammed , Rabaan Ali A.
Published: May 2024

Background

Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations.

Methods

A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3).

Results

The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8–42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2–62.4) in the eastern regions and 19.8% (95% CI: 10.8–33.4) in the western regions. No evidence of publication bias was detected.

Conclusion

The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.
A network analysis of exhaustion disorder symptoms throughout treatment
Authors: Mårtensson Gustav , Johansson Fred , Buhrman Monica , Åhs Fredrik , Clason van de Leur Jakob
Published: May 2024

Background

Stress-induced Exhaustion Disorder (ED) is associated with work absenteeism and adverse health outcomes. Currently, little is known regarding how the symptoms of ED are interrelated and whether the patterns of symptoms influence treatment outcomes. To this end, the current study applied network analyses on ED patients participating in a multimodal intervention.

Methods

The first aim of the study was to explore the internal relationships between exhaustion symptoms and identify symptoms that were more closely related than others. A second aim was to examine whether the baseline symptom network of non-responders to treatment was more closely connected than the baseline symptom networks of responders, by comparing the sum of all absolute partial correlations in the respective groups’ symptom network. This comparison was made based on the hypothesis that a more closely connected symptom network before treatment could indicate poorer treatment outcomes. Network models were constructed based on self-rated ED symptoms in a large sample of patients (n = 915) participating in a 24-week multimodal treatment program with a 12-month follow-up.

Results

The internal relations between self-rated exhaustion symptoms were stable over time despite markedly decreased symptom levels throughout participation in treatment. Symptoms of limited mental stamina and negative emotional reactions to demands were consistently found to be the most closely related to other ED symptoms. Meanwhile, sleep quality and irritability were weakly related to other exhaustion symptoms. The symptom network for the full sample became significantly more closely connected from baseline to the end of treatment and 12-month follow-up. The symptom network of non-responders to treatment was not found to be more closely connected than the symptom network of responders at baseline.

Conclusions

The results of the current study suggest symptoms of limited mental stamina and negative emotional reactions to demands are central ED symptoms throughout treatment, while symptoms of irritability and sleep quality seem to have a weak relation to other symptoms of ED. The implications of these findings are discussed in relation to the conceptualization, assessment, and treatment of ED.

Trial registration

The clinical trial was registered on Clinicaltrials.gov 2017-12-02 (Identifier: NCT03360136).
#Bartender: portrayals of popular alcohol influencer’s videos on TikTok©
Authors: Guégan Erell , Zenone Marco , Mialon Mélissa , Gallopel-Morvan Karine
Published: May 2024

Background

Despite widespread use of the short-video social media platform TikTok©, limited research investigates how alcohol is portrayed on the platform. Previous research suggests that a driver of alcohol content on TikTok©, in part, comes from bartenders demonstrating how to make drinks. This study aims to explore the characterizing patterns of how bartender influencers on TikTok© feature and incorporate alcohol in their videos.

Methods

We identified the global top 15 most followed bartenders on TikTok© in 2021 (cumulative 29.7 million subscribers) and the videos they posted in November and December 2021, the period just before Christmas and New Year, when alcohol tends to be more marketed than in other periods. The videos were coded based on five criteria: (1) the presence of alcohol or not; (2) alcohol categories; (3); alcohol brand(s) if visible; (4) the presence of candies and other sweet products; (5) presence of cues that refer to young people’s interests.

Results

In total, we identified 345 videos, which received 270,325,600 views in total, with an average of 18,021,707 views per video. Among these 345 videos, 92% (n = 317) displayed alcohol in their cocktail recipes (249,275,600 views, with an average of 786,358 views). The most common types of alcohol present in videos were liquor, vodka, rum, and whiskey, all of which are high-ABV beverages. 73% (n = 230) displayed or mentioned an alcohol brand. 17% (n = 55) associated alcohol with sweet products such as different types of candy (53,957,900 views, with an average of 981,053 views per video). 13% (n = 43) contained cues appealing to young people (e.g., cartoons, characters) (15,763,300 views, with an average of 366,588 views per video).

Conclusions

Our findings suggest a large presence of positively framed alcohol content posted by popular bartenders on TikTok©. As exposure to digital marketing is related to an increase in alcohol consumption, particularly among young people, regulations are needed to protect the public from alcohol-related harms.
Exploring the working life of people with multiple sclerosis during the COVID-19 pandemic in Sweden
Authors: Murley Chantelle , Dervish Jessica , Machado Alejandra , Svärd Veronica , Wennman-Larsen Agneta , Hillert Jan , Friberg Emilie
Published: May 2024

Background

The COVID-19 pandemic led to vast changes in working life and conditions in which we work. These changes may affect people with multiple sclerosis (PwMS) differently. We aimed to describe the working situation of PwMS during the COVID-19 pandemic and the pandemic’s impact on their working lives.

Methods

All individuals aged 20–50 listed in the Swedish Multiple Sclerosis Registry were invited to participate in an online survey in 2021. Closed and open-ended responses linked to individual-level register data were used in this exploratory mixed-methods study. Differences in the proportions reporting specific impacts were assessed with chi-square tests by sex, MS severity, education, and profession. The open-ended answers were analysed through content analysis.

Results

Over 8500 PwMS were invited (52% response rate). We included the 3887 respondents who answered questions about the impact of the pandemic on working life. Most (93.7%) reported being in paid work. An impact of the ongoing pandemic to one’s daily occupation was reported by 26.2%, with different characteristics observed across the impacts. Four categories of type of answers were identified from the open-ended answers: Direct impact on one’s occupation, Disclosing or concealing MS in the workplace, Worry and uncertainty, and Broader impact to life situation.

Conclusions

PwMS navigated the pandemic by interrupting as well as continuing their working lives. Many PwMS reported that the pandemic did not affect their work situation. However, the reported impacts differed among the participants and a sense of uncertainty and worry was often underlying their statements. Lessons from the pandemic may support future work participation.
The concept of intersectionality in bioethics: a systematic review
Authors: Brünig Lisa , Kahrass Hannes , Salloch Sabine
Published: May 2024

Background

Intersectionality is a concept that originated in Black feminist movements in the US-American context of the 1970s and 1980s, particularly in the work of feminist scholar and lawyer Kimberlé W. Crenshaw. Intersectional approaches aim to highlight the interconnectedness of gender and sexuality with other social categories, such as race, class, age, and ability to look at how individuals are discriminated against and privileged in institutions and societal power structures. Intersectionality is a “traveling concept”, which also made its way into bioethical research.

Methods

We conducted a systematic review to answer the question of where and how the concept of intersectionality is applied in bioethical research. The PubMed and Web of Science databases were systematically searched and 192 articles addressing bioethical topics and intersectionality were finally included.

Results

The qualitative analysis resulted in a category system with five main categories: (1) application purpose and function, (2) social dimensions, (3) levels, (4) health-care disciplines and academic fields, and (5) challenges, limitations, and critique. The variety of academic fields and health-care disciplines working with the concept ranges from psychology, through gynaecology to palliative care and deaf studies. Important functions that the concept of intersectionality fulfils in bioethical research are making inequities visible, creating better health data collections and embracing self-reflection. Intersectionality is also a critical praxis and fits neatly into the overarching goal of bioethics to work toward social justice in health care. Intersectionality aims at making research results relevant for respective communities and patients, and informs the development of policies.

Conclusions

This systematic review is, to the best of our knowledge, the first one to provide a full overview of the reference to intersectionality in bioethical scholarship. It creates a basis for future research that applies intersectionality as a theoretical and methodical tool for analysing bioethical questions.
30 years of youth system of care lessons learned – a qualitative study of Hawaiʻi’s partnership with the Substance Abuse and Mental Health Services Administration
Authors: Okamura Kelsie H. , Jackson David , Ching Danielle L. Carreira , Suh Da Eun , Hartsock Tia L. R. , Hee Puanani J. , Shimabukuro Scott K.
Published: May 2024

Background

The Hawaiʻi State Department of Health, Child and Adolescent Mental Health Division (CAMHD) has maintained a longstanding partnership with Substance Abuse and Mental Health Services Administration (SAMHSA) to enhance capacity and quality of community-based mental health services. The current study explored CAMHD’s history of SAMHSA system of care (SOC) awards and identified common themes, lessons learned, and recommendations for future funding.

Methods

Employing a two-phase qualitative approach, the study first conducted content analysis on seven final project reports, identifying themes and lessons learned based on SOC values and principles. Subsequently, interviews were conducted with 11 system leaders in grant projects and SOC award projects within the state. All data from project reports and interview transcripts were independently coded and analyzed using rapid qualitative analysis techniques.

Results

Content validation and interview coding unveiled two content themes, interagency collaboration and youth and family voice, as areas that required long-term and consistent efforts across multiple projects. In addition, two general process themes, connection and continuity, emerged as essential approaches to system improvement work. The first emphasizes the importance of fostering connections in family, community, and culture, as well as within workforce members and child-serving agencies. The second highlights the importance of nurturing continuity throughout the system, from interagency collaboration to individual treatment.

Conclusions

The study provides deeper understanding of system of care evaluations, offering guidance to enhance and innovate youth mental health systems. The findings suggest that aligning state policies with federal guidelines and implementing longer funding mechanisms may alleviate administrative burdens.
Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support
Authors: Ushimaru Yuki , Nagano Shinnosuke , Kawabata Ryohei , Nishikawa Kazuhiro , Takeoka Tomohira , Kitagawa Akihiro , Ohara Nobuyoshi , Tomihara Hideo , Maeda Sakae , Imasato Mitsunobu , Noura Shingo , Miyamoto Atsushi
Published: May 2024

Background

As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients.

Methods

A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes.

Results

Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications.

Conclusion

Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.
FruitPhenoBox – a device for rapid and automated fruit phenotyping of small sample sizes
Authors: Kirchgessner Norbert , Hodel Marius , Studer Bruno , Patocchi Andrea , Broggini Giovanni A. L.
Published: May 2024

Background

Fruit appearance of apple (Malus domestica Borkh.) is accession-specific and one of the main criteria for consumer choice. Consequently, fruit appearance is an important selection criterion in the breeding of new cultivars. It is also used for the description of older varieties or landraces. In commercial apple production, sorting devices are used to classify large numbers of fruit from a few cultivars. In contrast, the description of fruit from germplasm collections or breeding programs is based on only a few fruit from many accessions and is mostly performed visually by pomology experts. Such visual ratings are laborious, often difficult to compare and remain subjective.

Results

Here we report on a morphometric device, the FruitPhenoBox, for automated fruit weighing and appearance description using computer-based analysis of five images per fruit. Recording of approximately 100 fruit from each of 15 apple cultivars using the FruitPhenoBox was rapid, with an average handling and recording time of less than eleven seconds per fruit. Comparison of fruit images from the 15 apple cultivars identified significant differences in shape index, fruit width, height and weight. Fruit shape was characteristic for each cultivar, while fruit color showed larger variation within sample sets. Assessing a subset of 20 randomly selected fruit per cultivar, fruit height, width and weight were described with a relative margin of error of 2.6%, 2.2%, and 6.2%, respectively, calculated from the mean value of all available fruit.

Conclusions

The FruitPhenoBox allows for the rapid and consistent description of fruit appearance from individual apple accessions. By relating the relative margin of error for fruit width, height and weight description with different sample sizes, it was possible to determine an appropriate fruit sample size to efficiently and accurately describe the recorded traits. Therefore, the FruitPhenoBox is a useful tool for breeding and the description of apple germplasm collections.
Region-specific activation in the accumbens nucleus by itch with modified scratch efficacy in mice – a model-free multivariate analysis
Authors: Inokuchi-Sakata Sanae , Narita Ryo , Takahashi Yukari , Ishiuji Yozo , Asahina Akihiko , Kato Fusao
Published: May 2024

Itch is a protective/defensive function with divalent motivational drives. Itch itself elicits an unpleasant experience, which triggers the urge to scratch, relieving the itchiness. Still, it can also result in dissatisfaction when the scratch is too intense and painful or unsatisfactory due to insufficient scratch effect. Therefore, it is likely that the balance between the unpleasantness/pleasure and satisfaction/unsatisfaction associated with itch sensation and scratching behavior is determined by complex brain mechanisms. The physiological/pathological mechanisms underlying this balance remain largely elusive. To address this issue, we targeted the "reward center" of the brain, the nucleus accumbens (NAc), in which itch-responsive neurons have been found in rodents. We examined how neurons in the NAc are activated or suppressed during histamine-induced scratching behaviors in mice. The mice received an intradermal injection of histamine or saline at the neck, and the scratching number was analyzed by recording the movement of the bilateral hind limbs for about 45 min after injection. To experimentally manipulate the scratch efficacy in these histamine models, we compared histamine's behavioral and neuronal effects between mice with intact and clipped nails on the hind paws. As expected, the clipping of the hind limb nail increased the number of scratches after the histamine injection. In the brains of mice exhibiting scratching behaviors, we analyzed the expression of the c-fos gene (Fos) as a readout of an immediate activation of neurons during itch/scratch and dopamine receptors (Drd1 and Drd2) using multiplex single-molecule fluorescence in situ hybridization (RNAscope) in the NAc and surrounding structures. We performed a model-free analysis of gene expression in geometrically divided NAc subregions without assuming the conventional core–shell divisions. The results indicated that even within the NAc, multiple subregions responded differentially to various itch/scratch conditions. We also found different clusters with neurons showing similar or opposite changes in Fos expression and the correlation between scratch number and Fos expression in different itch/scratch conditions. These regional differences and clusters would provide a basis for the complex role of the NAc and surrounding structures in encoding the outcomes of scratching behavior and itchy sensations.
Critical reappraisal of short-acting bronchodilators for pediatric respiratory diseases
Authors: Licari Amelia , Manti Sara , Mastellone Francesco , Miraglia Del Giudice Michele , Marseglia Gian Luigi , Tosca Maria Angela ,   Asthma and Personalized Therapies Committee of the Italian Society of Pediatric Allergy & Immunology (SIAIP), Andrenacci Beatrice , Capristo Carlo , Cutrera Renato , Di Cicco Maria Elisa , Fierro Vincenzo , Leone Maddalena , Naso Matteo , Pezone Ilaria , Trincianti Chiara
Published: May 2024

Short-acting bronchodilators are a class of medications commonly used to treat asthma, chronic obstructive pulmonary disease, and other respiratory conditions. The use of these medications has evolved over time as we have gained a better understanding of their effectiveness and safety in the pediatric population. This comprehensive review synthesizes the current understanding of short-acting β2-agonists and short-acting anticholinergics in children. It addresses indications, contraindications, safety considerations, and highlights areas where further research is needed to guide the most effective use of short-acting bronchodilators.
Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure
Authors: Demoule Alexandre , Baptiste Amandine , Thille Arnaud W. , Similowski Thomas , Ragot Stephanie , Prat Gwénael , Mercat Alain , Girault Christophe , Carteaux Guillaume , Boulain Thierry , Perbet Sébastien , Decavèle Maxens , Belin Lisa , Frat Jean-Pierre ,   from the REVA Network (Research Network in Mechanical Ventilation)
Published: May 2024

Background

Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population.

Methods

This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality.

Results

At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16–65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40–64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046).

Conclusions

In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality.

Trial registration: clinicaltrials.gov Identifier # NCT 01320384.
Identification of the RSX interactome in a marsupial shows functional coherence with the Xist interactome during X inactivation
Authors: McIntyre Kim L. , Waters Shafagh A. , Zhong Ling , Hart-Smith Gene , Raftery Mark , Chew Zahra A. , Patel Hardip R. , Graves Jennifer A. Marshall , Waters Paul D.
Published: May 2024

The marsupial specific RSX lncRNA is the functional analogue of the eutherian specific XIST, which coordinates X chromosome inactivation. We characterized the RSX interactome in a marsupial representative (the opossum Monodelphis domestica), identifying 135 proteins, of which 54 had orthologues in the XIST interactome. Both interactomes were enriched for biological pathways related to RNA processing, regulation of translation, and epigenetic transcriptional silencing. This represents a remarkable example showcasing the functional coherence of independently evolved lncRNAs in distantly related mammalian lineages.
Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling
Authors: Liu Zi-Yang , Li Yuan-Quan , Wang Die-Lin , Wang Ying , Qiu Wan-Ting , Qiu Yu-Yang , Zhang He-Lin , You Qiang-Long , Liu Shi-min , Liang Qiu-Ni , Wu Er-Jian , Hu Bing-Jie , Sun Xiang-Dong
Published: May 2024

Background

Human patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear.

Methods

Lrp4f/fmice were crossed withhGFAP-CreandNex-Cremice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4−/−) and pyramidal neuron specific knockout mice (Nex-Lrp4−/−). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored.

Results

We found thatLrp4deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice withLrp4deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE.

Conclusion

These results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.
Information and communication technology in SMEs: a systematic literature review
Authors: Yuwono Tri , Suroso Agus , Novandari Weni
Published: May 2024

The adoption of information and communication technology (ICT) in small- and medium-sized firms (SMEs) is steadily increasing. However, the implementation of ICT in SMEs is hindered by constraints, such as limited financial resources, lack of ICT knowledge, and reluctance to change. The objective of this study is to identify and analyze prevalent patterns, obstacles and influences that impact the adoption of ICT in SMEs in developing nations. In addition, this study aims to provide recommendations on the most effective methods to optimize the utilization of ICT in these contexts. This review is conducted using a sample of 25 publications that have been published and are available in the Scopus database. The selection process focuses on works that have received significant citations and have been published between 2014 and 2023. The PRISMA statement form was utilized to elucidate the comprehensive procedure of selecting and accepting pertinent publications. This research makes two distinct contributions. The writers begin by doing a thorough literature analysis to examine the progress of ICT in the past decade. They next emphasize noteworthy research discoveries in this field. Furthermore, the authors give a comprehensive analysis of the ICT literature by quantifying yearly publications and identifying SMEs that primarily utilize ICT, academic journals that publish pertinent articles, and ICT-related publications across various fields and areas in developing nations. The study also discloses the papers, journals, and authors that have received the highest number of citations. The author's final argument in the paper is that, despite the extensive research conducted in the field of ICT, there is a necessity to customize strategies and policies that can support SMEs in the ICT sector, particularly in developing countries.