bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty assessment tools and their predictive value in preoperative evaluation for general surgery: a narrative review
Authors: Cardoso Swizel Ann , Suyambu Jenisha , Amin Aamir , Iqbal Javed , Cardoso Rayner Peyser , Iqbal Ather , Bal Akarshak , Varghese Isaac Natasha , Raufi Nahid
Published: June 2024

The world’s population is ageing rapidly, with projections suggesting a significant increase in the elderly demographic over the next few decades. This shift is likely to result in long periods of infirmity and frailty, thus escalating healthcare demands. Frailty has been investigated almost exclusively in the elderly because of its association with the senior population. It is considered to be an unavoidable aspect of old age, rather than a variable aspect of ageing. It has been linked to a greater risk of falls and decreased mobility, increased hospitalizations, institutionalization, and mortality. Due to elevated complication risk, the frail group required expert surgical treatment and specialised care. Various models have been described in recent years, including the Frailty Phenotype model, the Edmonton Frailty scale, and the Clinical Frailty scale, among many others. Each model employs several components to assess an individual’s frailty. There is, however, no gold standard for measuring fragility. The use of such assessment methods in pre-operative frailty screening as a risk-stratification instrument has been shown to be effective in older persons undergoing general surgery. The use of frailty assessment tools to determine the level of frailty together with evidence-based treatment and management should be supported by collaborative decision making. In this narrative review, we discussed the four commonly used frailty assessment tools with a particular emphasis on the need for additional research to refine these models and enhance their predictive accuracy in surgical settings.
Tobacco Retail Sales in Massachusetts and New Hampshire Before and After Massachusetts' Flavored Tobacco Restriction
Authors: McGinnes Hannah , Kingsley Melody , Song Glory , Doane Jacqueline , Henley Patricia
Published: June 2024

In June 2020, Massachusetts became the first state to implement a comprehensive flavored tobacco restriction. One concern was that Massachusetts residents would travel to New Hampshire to purchase restricted products. This article assesses tobacco sales in both states post–law implementation. Retail scanner data were obtained from the Nielsen Company and Information Resources, Inc (IRI), from 1 year pre–law implementation to 2 years post–law implementation. Data post–law implementation were compared with data from 1 year pre–law implementation (baseline). In Massachusetts, 2 years post–law implementation, flavored and menthol tobacco sales decreased by more than 90%. Total sales decreased by around 20%. In New Hampshire, menthol tobacco sales increased (25.1% in IRI and 18.2% in Nielsen), but total sales changed minimally (<5% increase in IRI, <5% decrease in Nielsen). When data from both states were combined, total sales decreased by around 10%. The net decrease in total tobacco sales across Massachusetts and New Hampshire indicates Massachusetts' flavored tobacco restriction resulted in a reduction in tobacco sales despite potential cross-border purchases.
Evaluation of a Suspected Overdose Form for Timely Surveillance of Fatal Drug Overdoses, Multnomah County, OR, 2020-2021
Authors: Walters Jaime K. , Lewis Paul , Dileo Kim
Published: June 2024

Objectives:

There is a significant delay in finalization of drug overdose deaths, and a need to more quickly identify suspected overdoses to improve public health response. The objective of our study was to describe creation of a suspect overdose form and evaluate its use.

Design:

Evaluation of a suspected overdose form used to record information related to death investigation with matching to state vital records. We calculated the toxicology turnaround time for matched records, and also calculated sensitivity, specificity, positive predictive value, and negative predictive value of the form compared to vital records as the gold standard.

Setting:

Multnomah County, Oregon, deaths investigated by the County Medical Examiner between January 2020 and December 2021.

Main Outcome Measure:

Sensitivity of the suspected overdose form.

Results:

We analyzed 2818 matched death records in total during the study period. The average turnaround time for the 1673 records with toxicology results was 101 days. In 2020, sensitivity of the form was 74%, but this increased to nearly 95% in 2021.

Conclusions:

Multnomah County’s suspected evaluation form provides a timelier indicator of deaths suspected to be from drug overdose, has good sensitivity to detect true overdoses, and can help guide more rapid public health and public safety response activities.
Emergency Medical Services and Public Health Perspectives on Alternative Emergency Response Models
Authors: Miller Alison K. , Gage Christopher B. , Parrish Matthew , Toliver Isaac , Ulintz Alexander , Powell Jonathan , Frey Jennifer A. , Panchal Ashish R.
Published: June 2024

Context:

New approaches to emergency response are a national focus due to evolving needs and growing demands on the system, but perspectives of first responders and potential partners have not been evaluated.

Objective:

This project aimed to inform the development and implementation of alternative emergency response models, including interdisciplinary partnerships, by identifying the perspectives of the frontline workforce regarding their evolving roles.

Design:

An electronic survey was sent, querying respondents about their perceived roles in emergency response, interdisciplinary partnerships, and resources needed.

Setting:

This study took place in a metropolitan, midwestern county with participants from 2 public health agencies and 1 emergency medical services (EMS) agency.

Participants:

The survey was completed by 945 EMS clinicians and 58 public health workers.

Main Outcome Measures:

The main outcome measures were agreement levels on each group’s roles in prevention, response, and recovery after emergencies, as well as general feedback on new models.

Results:

Overall, 97% of EMS clinicians and 42% of public health workers agreed that they have a role in immediate response to 9-1-1 emergencies. In mental health emergencies, 87% of EMS clinicians and 52% of public health workers agreed that they have a role, compared to 87% and 30%, respectively, in violent emergencies. Also, 84% of respondents felt multidisciplinary models are a needed change. However, 35% of respondents felt their agency has the resources necessary for changes.

Conclusions:

We observed differences between EMS clinicians and public health workers in their perceived roles during emergency response and beliefs about the types of emergencies within their scope. There is strong support for alternative approaches and a perception that this model may improve personal well-being and job satisfaction, but a need for additional resources to develop and implement.
Understanding the Roles, Responsibilities, and Factors for Success of Health Equity Officers in Health Care Settings: A Qualitative Study
Authors: Adler Rachel R. , Pomer Alysa , Diviti Saathvika , Lewis Joy , Tan-McGrory Aswita , Weissman Joel S.
Published: June 2024

Context:

Recent national guidelines aimed at addressing equity in health care settings have contributed to an increase in equity officer positions, yet little is known about their roles, responsibilities, or strategies for engaging in health equity work.

Objective:

To understand the roles and responsibilities of equity officers, as well as facilitators and barriers to their success.

Design:

In-depth semi-structured interviews with selected respondents from the Equity Officer National Study.

Setting:

Hospitals and health care systems across the United States.

Participants:

Twenty-six equity officers who had responded to the Equity Officer National Study survey.

Main Outcome Measures:

The interview guide explored strategies, facilitators, and barriers for engaging in health equity work in hospitals/health systems and communities.

Results:

The job roles described by participants fell into 4 categories: community benefits/relations, population/community health, workforce, and health equity. Equity officers described key areas to support success at the individual equity officer level: knowledge and expertise, professional skills, and interpersonal skills; at the hospital level: leadership, workforce, infrastructure and resources, and policies and processes; at the community level: leadership and partnerships; and at the system level: requirements and regulations, investment and resources, and sociocultural and political characteristics of the community. These key areas have been organized to create a Framework for Equity Officer Success.

Conclusions:

The Framework for Equity Officer Success should be incorporated into hospital board, community stakeholder, and policymaker discussions about how to support health equity work in hospitals and health care systems.
Blood Gene Signature as a Biomarker for Subclinical Kidney Allograft Rejection: Where Are We?
Authors: Masset Christophe , Danger Richard , Degauque Nicolas , Dantal Jacques , Giral Magali , Brouard Sophie
Published: June 2024

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell–mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss. Paradoxically, the invasive characteristics and associated logistics of such procedures paved the way to investigate noninvasive biomarkers (urine and blood) of subclinical rejection. Among them, several research teams proposed a blood gene signature developed from cohort studies, most of which achieved excellent predictive values for the occurrence of subclinical rejection, mainly antibody-mediated rejection. Interestingly, although all identified genes relate to immune subsets and pathways involved in rejection pathophysiology, very few transcripts are shared among these sets of genes, highlighting the heterogenicity of such episodes and the difficult but mandatory need for external validation of such tools. Beyond this, their application and value in clinical practice remain to be definitively demonstrated in both biopsy avoidance and prevention of clinical rejection episodes. Their combination with other biomarkers, either epidemiological or biological, could contribute to a more accurate picture of a patient’s risk of rejection and guide clinicians in the follow-up of kidney transplant recipients.
The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients
Authors: Akabane Miho , Esquivel Carlos O. , Kim W. Ray , Sasaki Kazunari
Published: June 2024

Background.

The role of donor age in liver transplantation (LT) outcomes for hepatocellular carcinoma (HCC) is controversial. Given the significant risk of HCC recurrence post-LT, optimizing donor/recipient matching is crucial. This study reassesses the impact of young donors on LT outcomes in patients with HCC.

Methods.

A retrospective review of 11 704 LT cases from the United Network for Organ Sharing database (2012–2021) was conducted. The study focused on the effect of donor age on recurrence-free survival, using hazard associated with LT for HCC (HALT-HCC) and Metroticket 2.0 scores to evaluate post-LT survival in patients with HCC.

Results.

Of 4706 cases with young donors, 11.0% had HCC recurrence or death within 2 y, and 18.3% within 5 y. These outcomes were comparable with those of non-young donors. A significant correlation between donor age and post-LT recurrence or mortality (P = 0.04) was observed, which became statistically insignificant after tumor-related adjustments (P = 0.32). The Kaplan-Meier curve showed that recipients with lower HALT-HCC scores (<9) and Metroticket 2.0 scores (<2.2) significantly benefited from young donors, unlike those exceeding these score thresholds. Cox regression analysis showed that donor age significantly influenced outcomes in recipients below certain score thresholds but was less impactful for higher scores.

Conclusions.

Young donors are particularly beneficial for LT recipients with less aggressive HCC, as indicated by their HALT-HCC and Metroticket 2.0 scores. These findings suggest strategically allocating young donors to recipients with less aggressive tumor profiles, which could foster more efficient use of the scarce donor supply and potentially enhance post-LT outcomes.
Brown Adipose Tissue as a Unique Niche for Islet Organoid Transplantation: Insights From In Vivo Imaging
Authors: Sun Aixia , Hayat Hanaan , Kenyon Elizabeth , Quadri Tahnia , Amos Darius , Perkins Keenan , Nigam Saumya , Tarleton Deanna , Mallett Christiane L. , Deng Cheri X. , Qiu Zhen , Li Wen , Sempere Lorenzo , Fan Jinda , Aguirre Aitor , Wang Ping
Published: June 2024

Background.

Transplantation of human-induced pluripotent stem cell (hiPSC)-derived islet organoids is a promising cell replacement therapy for type 1 diabetes (T1D). It is important to improve the efficacy of islet organoids transplantation by identifying new transplantation sites with high vascularization and sufficient accommodation to support graft survival with a high capacity for oxygen delivery.

Methods.

A human-induced pluripotent stem cell line (hiPSCs-L1) was generated constitutively expressing luciferase. Luciferase-expressing hiPSCs were differentiated into islet organoids. The islet organoids were transplanted into the scapular brown adipose tissue (BAT) of nonobese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice as the BAT group and under the left kidney capsule (KC) of NOD/SCID mice as a control group, respectively. Bioluminescence imaging (BLI) of the organoid grafts was performed on days 1, 7, 14, 28, 35, 42, 49, 56, and 63 posttransplantation.

Results.

BLI signals were detected in all recipients, including both the BAT and control groups. The BLI signal gradually decreased in both BAT and KC groups. However, the graft BLI signal intensity under the left KC decreased substantially faster than that of the BAT. Furthermore, our data show that islet organoids transplanted into streptozotocin-induced diabetic mice restored normoglycemia. Positron emission tomography/MRI verified that the islet organoids were transplanted at the intended location in these diabetic mice. Immunofluorescence staining revealed the presence of functional organoid grafts, as confirmed by insulin and glucagon staining.

Conclusions.

Our results demonstrate that BAT is a potentially desirable site for islet organoid transplantation for T1D therapy.
Whole genome sequence of Paracoccus sp. NFXS7, a carotenoid-producing bacterium isolated from a marine saltern
Authors: Bertrand Constança , Martins Rodrigo , Quintas-Nunes Francisco , Reynolds-Brandão Pedro , Barreto Crespo Maria , Nascimento Francisco X
Published: June 2024

The whole genome sequence of the carotenoid-producing Paracoccus sp. NFXS7, isolated from a marine saltern in Setúbal, Portugal, is presented herein. The carotenoid-producing strain NFXS7 contains homologs of the crt genes involved in astaxanthin biosynthesis, making it a promising candidate for biotechnological applications.
Detecting accelerated retinal decline in mental disorders through normative modeling
Authors: Georgiadis Foivos , Kallen Nils , Cecere Giacomo , Rabe Finn , Edkins Victoria , Barthelmes Daniel , Roguski Amber , Smith Daniel , Kirschner Matthias , Homan Philipp
Published: June 2024

Objective

Several studies have found thinner retinal tissue in mental disorders compared to healthy controls. Because the retina is part of the human brain, this suggests that informative brain structure readouts can be obtained efficiently through retinal imaging. Instead of focusing on group-level case-control differences, we used normative modeling to estimate age-related decline of the human retina (and its expected variation) and compared it to the decline seen in schizophrenia (SZ), bipolar disorder (BD), and major depression (MDD). We hypothesized accelerated retinal decline in mental disorders compared to controls, with SZ being most affected, followed by BD, then MDD.

Methods

Using UK Biobank data, we estimated age-related retinal decline in healthy controls (HC, N = 56,545) for total macular thickness (including coronal subfields) and two sublayers (retinal nerve fiber layer; RNFL; and ganglion cell-inner plexiform layer; GC-IPL). We then compared the decline in SZ (N = 171), BD (N = 256), and MDD (N = 102) to the normative decline in HC.

Results

For HC, the pattern of age-related decline for total macular thickness, RNFL, and GC-IPL was curve-like rather than linear and more pronounced in males compared to females. For mental disorders, the decline-pattern was generally faster, driven by SZ and disorder-specific macular subfields. There was also an enrichment of individuals with extremely low (infranormal) values. These results were confirmed in robustness checks that ruled out unspecific confounders.

Conclusion

These findings suggest that mental disorders, particularly SZ, involve accelerated neurodegenerative decline that can be detected in the human retina.
Did institutional racism contribute to adverse COVID-19 clinical outcomes in ethnic minority healthcare staff? Systematic review
Authors: Adewole Oluwatomisin , Lalli Kismet , Peters Holly , Price Chris , Lumb Blanche , Gal Micaela , Cooper Alison
Published: June 2024

Introduction

Of the United Kingdom National Health Service (NHS) healthcare workers who died during the first wave of the pandemic, 63% belonged to an ethnic minority background, despite making up 21% of the NHS workforce. Previous research has considered biological and social causes such as obesity or overcrowded housing. This review aims to explore whether elements of institutional racism contributed to ethnic disparities in adverse COVID-19 clinical outcomes among healthcare staff.

Method

Eleven databases were searched including MEDLINE and the Cochrane Library. Eight healthcare organisations within the grey literature were also searched. A narrative synthesis was conducted.

Results

20 studies were included for review. There were ethnic disparities in the rate of COVID-19 infection, mortality and wellbeing. Three elements of institutional racism were identified associated with these adverse outcomes, namely, overrepresentation of ethnic minority staff in frontline roles, discriminatory redeployment and harassment and bullying.

Conclusion

The pandemic exacerbated pre-existing racial inequalities within the UK healthcare workforce. Further research is required to clarify the definition of institutional racism and increase understanding of how this manifests in a healthcare setting and can be mitigated.

Funding statement

The Wales COVID-19 Evidence Centre was funded for this work by Health and Care Research Wales on behalf of Welsh Government.
Background and Foreground: Connections & Distinctions when Health Professions Faculty Teach Both Interprofessional Collaborative Practice and Quality Improvement – A Case Study
Authors: Stevenson Katherine , Thor Johan , D’Eon Marcel , Headrick Linda A. , Gäre Boel Andersson
Published: June 2024

Despite decades of effort, programs continue to struggle to integrate competencies related quality improvement (QI) and interprofessional collaborative practice (ICP) into health professions education. Additionally, while QI and ICP may seem intuitively linked and there exists some examples of a coordinated approach, the literature regarding competencies, including knowledge, skills, and attitudes (KSAs), is still largely focused on QI and ICP as separate fields of knowledge and practice. This study explored distinctions and connections between quality improvement (QI) and interprofessional collaborative practice (ICP) competency domains in health professions education. The authors used a qualitative case study approach with an instrumental case, i.e., the University of Missouri-Columbia (MU), where QI and ICP were intentionally integrated as part of core curricula in health professional schools and programs. Eleven faculty members from medicine, nursing, pharmacy, and health care administration participated in interviews exploring their teaching choices in either classroom or clinical settings. Study participants defined the goal of teaching QI and ICP as enabling learners to deliver safe and patient-centered care and described the knowledge and skills required for QI and the attitudes and skills required for ICP. Furthermore, they described the relationship between QI and ICP as one mediated by systems thinking, where ICP is backgrounded as a critical pre-requisite and QI is foregrounded as a vector for developing interprofessional competencies. The MU case elucidates the potential synergies that occur when faculty address quality improvement and interprofessional collaborative practice competencies with an integrated approach that leverages connections, while also respecting distinctions. For health professions education programs looking to improve the effectiveness and efficiency of their curricular approach to these fields, it may be fruitful to consider ICP as background and QI as foreground, remembering that without each other, ICP risks losing meaning and QI risks losing impact.
Exploring Kp,uu,BBB Values Smaller than Unity in Remoxipride: A Physiologically-Based CNS Model Approach Highlighting Brain Metabolism in Drugs with Passive Blood-Brain Barrier Transport
Authors: Zhang Mengxu , Vuist Ilona M. , Rottschäfer Vivi , de Lange Elizabeth CM
Published: June 2024

(Aim)

Kp,uu,BBBvalues are crucial indicators of drug distribution into the brain, representing the steady-state relationship between unbound concentrations in plasma and in brain extracellular fluid (brainECF). Kp,uu,BBBvalues < 1 are often interpreted as indicators of dominant active efflux transport processes at the blood-brain barrier (BBB). However, the potential impact of brain metabolism on this value is typically not addressed. In this study, we investigated the brain distribution of remoxipride, as a paradigm compound for passive BBB transport with yet unexplained brain elimination that was hypothesized to represent brain metabolism.

(Methods)

The physiologically-based LeiCNS pharmacokinetic predictor (LeiCNS-PK model) was used to compare brain distribution of remoxipride with and without Michaelis-Menten kinetics at the BBB and/or brain cell organelle levels. To that end, multiple in-house (IV 0.7, 3.5, 4, 5.2, 7, 8, 14 and 16 mg/kg) and external (IV 4 and 8 mg/kg) rat microdialysis studies plasma and brainECF data were analysed.

(Results)

The incorporation of active elimination through presumed brain metabolism of remoxipride in the LeiCNS-PK model significantly improved the prediction accuracy of experimentally observed brainECF profiles of this drug. The model integrated with brain metabolism in both barriers and organelles levels is named LeiCNS-PK3.5.

(Conclusion)

For drugs with Kp,uu,BBBvalues < 1, not only the current interpretation of dominant BBB efflux transport, but also potential brain metabolism needs to be considered, especially because these may be concentration dependent. This will improve the mechanistic understanding of the processes that determine brain PK profiles.
Identification of non-charged 7.44 analogs interacting with the NHR2 domain of RUNX1-ETO and exhibiting an improved, selective antiproliferative effect in RUNX-ETO positive cells
Authors: Gopalswamy Mohanraj , Bickel David , Dienstbier Niklas , Tu Jia-Wey , Schott-Verdugo Stephan , Bhatia Sanil , Etzkorn Manuel , Gohlke Holger
Published: June 2024

The RUNX1/ETO fusion protein is a chimeric transcription factor in acute myeloid leukemia (AML) created by chromosomal translocation t(8;21)(q22;q22). t(8;21) abnormality is associated with 12% ofde novoAML cases and up to 40% in the AML subtype M2. Previously, we identified the small-molecule inhibitor7.44, which specifically interferes with NHR2 domain tetramerization of RUNX1/ETO, restores gene expression down-regulated by RUNX1/ETO, inhibits proliferation, and reduces RUNX1/ETO-related tumor growth in a mouse model. However, despite generally favorable physicochemical, pharmacokinetic, and toxicological properties,7.44is negatively charged at physiological pH and was predicted to have low to medium membrane permeability. Here, we identifiedM23,M27,andM10as non-charged analogs of7.44using ligand-based virtual screening,in vivohit identification, biophysical andin vivohit validation, and integrative modeling and ADMET predictions. All three compounds interact with the NHR2 domain and showKD,appvalues of 39-114 µM in Microscale Thermophoresis experiments as well asIC50values of 33-77 μM as to cell viability in RUNX1/ETO-positive KASUMI cells, i.e., are ∼5 to 10-fold more potent than7.44.M23is ∼10-fold more potent than7.44in inhibiting cell proliferation of RUNX1/ETO-positive cells.M23andM27are negligibly protonated or in a ∼1:1 ratio at physiological pH, whileM10has no (de-)protonatable group. The non-protonated species are predicted to be highly membrane-permeable, along with other favorable pharmacokinetic and toxicological properties. These compounds might serve as lead structures for the optimization of binding affinity, bioavailability, and anti-leukemic effects of compounds inhibiting RUNX1/ETO oncogenic function in t(8;21) AML.
Lipid droplets restrict phagosome formation duringCandidachallenge
Authors: Sun Wanwei , Wu Han , Zhao Guimin , Shui Qing , Zhang Lei , Luan Xiaoxi , Chen Tian , Liu Feng , Zheng Yi , Zhao Wei , Qi Xiaopeng , Liu Bingyu , Gao Chengjiang
Published: June 2024

Lipid droplets (LDs) are intracellular organelles which can be induced and interact with phagosomes during the process of pathogen phagocytosis in macrophages. However, the function of LDs in the phagocytosis remains elusive. Here, we unveil the role of LDs in modulating phagosome formation using a fungal infection model. Specifically, LDs accumulation restricted the quantity of phagosome formation, and protected macrophages from death. Mechanistically, LDs formation competitively consumed intracellular endoplasmic reticulum membrane and altered RAC1 translocation and its GTPase activity, which resulted in limiting phagosomes formation in macrophages during fungi engulfed. Mice withHilpda-deficient macrophages were more susceptible to the lethal sequelae of systemic infection withC. albicans. Notably, administration of ATGL inhibitor Atglistatin improved host outcomes in disseminated fungal infections. Taken together, our study elucidates the mechanism of LDs in controlling phagosomes formation to avoid immune cell death, and offers a potential drug target for treatment ofC. albicansinfections.

Highlights

C. albicansinfection induces triglycerides production and LD accumulation in macrophages.

LD restricts the quantity of phagosome formation and protects macrophages from death.

LD consumes intracellular ER membrane components and alters RAC1 translocation and its GTPase activity.

Administration of ATGL inhibitor Atglistatin improves host outcomes in disseminated fungal infections.
Barriers and facilitators of Highly Active Antiretroviral Therapy (HAART) adherence among HIV-positive Women in Southern Ethiopia: A Qualitative study
Authors: Demissie Alemayehu Abebe , Rensburg Elsie Janse van
Published: June 2024

Background

Adherence to Highly Active Antiretroviral Therapy (HAART) medication is the major predictor of HIV/AIDS treatment success. Poor adherence to HAART creates the risk of transmitting HIV, deteriorating health conditions, treatment failure, increased occurrences of drug-resistant HIV, morbidity and mortality. The objective of this study was to explore and describe the experiences of HAART adherence among HIV-positive women in Southern Ethiopia.

Methods

Semi-structured in-depth interviews (IDIs) were conducted with 12 HIV-positive women in Southern Ethiopia who are adhering and non-adhering to HAART. Interviews were conducted in the local Amharic language and audio recorded with permission from the participants. The interviews were transcribed verbatim, coded for themes, categories and sub-categories and analyzed using a thematic data analysis technic.

Results

The findings of the study reflected two themes: barriers and facilitators of HAART medication adherence among HIV-positive women. Barriers and facilitators were further categorized into 5 categories. These included patient-related factors, treatment-related factors, psychosocial-related factors, family and community-related factors, and healthcare services-related factors. These categories were further divided into 22 sub-categories. Busy schedule, forgetting the doses, rituals of religion, economic constraints, drug side-effects, pills burden and size, misconceptions about HIV, negative attitudinal disposition towards HAART, refusal to adhere to HAART, depression, lack of hope and courage, stigma and discrimination, relationship with healthcare providers, a working day of HAART clinic, and long waiting time were identified as barriers to HAART adherence. While, family responsibilities, reminder devices, dosage formulation, perceived benefit of HAART, family support, adherence to supporting peer groups, and adherence to counselling/education were identified as facilitators of HAART adherence.

Conclusions

Adherence to HAART medication is a major challenge among HIV-positive women in Southern Ethiopia. Therefore, tailored strategies to enhance HAART medication adherence should be targeted addressing the barriers identified in the study.
Long-term outcomes of TAVI patients undergoing different pacing modality: LBBAP versus RVP
Authors: Wang Xi , Xu Yuanning , Zeng Lijun , Tan Kun , Zhang Xueli , Han Xu , Xiong Tianyuan , Zhao Zhengang , Peng Yong , Wei Jiafu , Li Qiao , He Sen , Chen Yong , Zhou Minggang , Li Xi , Wei Xin , Liang Yujia , Zhou Wenxia , Jiang Lingyun , Liu Xingbin , Meng Wei , Zhou Rui , Xiong Guojun , Dai Min , Deng Xiaojian , Feng Yuan , Chen Mao
Published: June 2024

Background

New-onset permanent pacemaker implantation (PPMI) is still a common complication after transcatheter aortic valve implantation (TAVI) with adverse clinical outcomes. This study aims to investigate whether left bundle branch area pacing (LBBAP) improves long-term clinical results compared to traditional right ventricular pacing (RVP) in patients requiring PPMI following TAVI.

Methods

A total of 237 consecutive patients undergoing RVP (N=117) or LBBAP (N=120) following TAVI were retrospectively included. Long-term outcomes including all-cause death, heart failure rehospitalization (HFH) and left ventricular ejection fraction (LVEF) change compared to baseline were obtained until 5 years post-TAVI.

Results

The mean age of the overall population was 74 years with a mean surgical risk score as 4.4%. The paced QRS duration was significantly shorter in LBBAP group compared to RVP group (151 ± 18 vs. 122 ±12 ms, P<0.001). There was no difference between two groups in all-cause death (13.7% vs. 13.3%, adjusted HR: 0.76; 95% CI: 0.37 to 1.58; P=0.466) or the composite endpoint of death and HFH (29.9% vs. 19.2%, adjusted HR: 1.22; 95% CI: 0.70 to 2.13; P=0.476), however, the risk of HFH was significantly reduced in LBBAP group compared to RVP at 5 years after TAVI (21.4% vs. 7.5%, adjusted HR: 2.26; 95% CI: 1.01 to 5.08; P=0.048). There was a more marked evolution of LVEF over time in LBBAP group (P=0.046 for LVEF changes over time between groups).

Conclusions

LBBAP improved long-term clinical outcomes compared to RVP in patients undergoing PPMI after TAVI in terms of less HFH and better LVEF improvement.
Predicting the effort required to manually mend auto-segmentations
Authors: He Da , Udupa Jayaram K. , Tong Yubing , Torigian Drew A.
Published: June 2024

Auto-segmentation is one of the critical and foundational steps for medical image analysis. The quality of auto-segmentation techniques influences the efficiency of precision radiology and radiation oncology since high-quality auto-segmentations usually require limited manual correction. Segmentation metrics are necessary and important to evaluate auto-segmentation results and guide the development of auto-segmentation techniques. Currently widely applied segmentation metrics usually compare the auto-segmentation with the ground truth in terms of the overlapping area (e.g., Dice Coefficient (DC)) or the distance between boundaries (e.g., Hausdorff Distance (HD)). However, these metrics may not well indicate the manual mending effort required when observing the auto-segmentation results in clinical practice.

In this article, we study different segmentation metrics to explore the appropriate way of evaluating auto-segmentations with clinical demands. The mending time for correcting auto-segmentations by experts is recorded to indicate the required mending effort. Five well-defined metrics, the overlapping area-based metric DC, the segmentation boundary distance-based metric HD, the segmentation boundary length-based metrics surface DC (surDC) and added path length (APL), and a newly proposed hybrid metric Mendability Index (MI) are discussed in the correlation analysis experiment and regression experiment. In addition to these explicitly defined metrics, we also preliminarily explore the feasibility of using deep learning models to predict the mending effort, which takes segmentation masks and the original images as the input.

Experiments are conducted using datasets of 7 objects from three different institutions, which contain the original computed tomography (CT) images, the ground truth segmentations, the auto-segmentations, the corrected segmentations, and the recorded mending time. According to the correlation analysis and regression experiments for the five well-defined metrics, the variety of MI shows the best performance to indicate the mending effort for sparse objects, while the variety of HD works best when assessing the mending effort for non-sparse objects. Moreover, the deep learning models could well predict efforts required to mend auto-segmentations, even without the need of ground truth segmentations, demonstrating the potential of a novel and easy way to evaluate and boost auto-segmentation techniques.
UV LED Wastewater Disinfection: The Future is Upon Us Full-scale installation and auditing of 280nm UV LED disinfection reactor
Authors: MacIsaac Sean A , Reid Bailey , Ontiveros Carolina , Linden Karl G , Stoddart Amina K , Gagnon Graham A
Published: June 2024

The world’s first full-scale, 280 nm UV LED reactor for wastewater disinfection was tested at flows of 545 and 817 m3day-1. The system achieved a >3 average log reduction of total coliform at 545 m3day-1and the 817 m3day-1flow rate achieved over a >2.5 average log reduction for all operational conditions. The delivered fluence of the full-scale system ranged from 28-148 mJ cm-2and aligns with a UV auditing study that was conducted prior to the installation of the wastewater reactor. These results benchmark the performance that can be achieved by UV LED disinfection and further connect bench-scale disinfection results with full-scale performance. The approach established in this manuscript provides a novel tool for utilities when considering emerging UV disinfection technologies. In summary, this study establishes that UV LEDs are an effective wastewater disinfectant at-scale and are comparable to conventional low-pressure UV systems. This is the first instance where the efficacy of UV LEDs for municipal wastewater disinfection has been demonstrated using a large-scale installation at a functioning wastewater facility.

Graphical Abstract
TBtypeR: Sensitive detection and sublineage classification of low-frequencyMycobacterium tuberculosiscomplex mixed infections
Authors: Munro Jacob E , Coussens Anna K , Bahlo Melanie
Published: June 2024

Mixed infections comprising multipleMycobacterium tuberculosisComplex (MTBC) strains are observed in populations with high incidence rates of tuberculosis (TB), yet the difficulty to detect these via conventional diagnostic approaches has resulted in their contribution to TB epidemiology and treatment outcomes being vastly underrecognised. In endemic regions, detection of all component strains is crucial for accurate reconstruction of TB transmission dynamics. Currently available tools for detecting mixed infections from whole genome sequencing (WGS) data have insufficient sensitivity to detect low-frequency mixtures with less than 10% minor strain fraction, leading to a systematic underestimation of the frequency of mixed infection. Our R package, TBtypeR, identifies mixed infections from whole genome sequencing by comparing sample data to an expansive phylogenetic SNP panel of over 10,000 sites and 164 MTBC strains. A statistical likelihood is derived for putative strain mixtures based on the observed reference and alternative allele counts at each site under the binomial distribution. This provides robust and high-resolution sublineage classification for both single- and mixed-infections with as low as 1% minor strain frequency. Benchmarking with simulatedin silicoandin vitromixture data demonstrates the superior performance of TBtypeR over existing tools, particularly in detecting low frequency mixtures. We apply TBtypeR to 5,000 MTBC WGS from a published dataset and find a 6-fold higher rate of mixed infection than existing methods. The TBtypeR R package and accompanying end-to-end Nextflow pipeline are available at github.com/bahlolab/TBtypeR.
A mechanism for telomere-specific telomere length regulation
Authors: Teplitz Gabriela M. , Pasquier Emeline , Bonnell Erin , Laurentiis Evelina De , Bartle Louise , Lucier Jean-François , Sholes Samantha , Greider Carol W. , Wellinger Raymund J.
Published: June 2024

Summary Paragraph

Telomeric DNA, composed of short, direct repeats, is of crucial importance for chromosome stability. Due to intrinsic problems with replicating this DNA, the repeat tracts shorten at each cell division. Once repeat tracts become critically short, a telomeric stress signal induces cellular senescence and division arrest, which eventually may lead to devastating age-related degenerative diseases associated with dysfunctional telomers. Conversely, maintenance of telomere length by telomerase upregulation is a hallmark of cancer. Therefore, telomere length is a critical determinant of telomere function. How telomere length is established and molecular mechanisms for telomere-specific length regulation remained unknown. Here we show that subtelomeric chromatin is a determinant for how telomere equilibrium set-length is established incis. The results demonstrate that telomerase recruitment mediated by the telomere-associated Sir4 protein is modulated on chromosome 3L in a telomere-specific way. Increased Sir4 abundance on subtelomeric heterochromatin of this specific telomere leads to telomere lengthening of only that telomere incis, but not at other telomeres. Therefore, this work describes a mechanism for a how telomere-specific repeat tract length can be established. Further, our results will force the evaluation of telomere length away from a generalized view to a more telomere-specific consideration.
ATF4 and mTOR regulate metabolic reprogramming in TGF-β-treated lung fibroblasts
Authors: Shin Kun Woo D , Atalay M Volkan , Cetin-Atalay Rengul , O’Leary Erin M , Glass Mariel E , Houpy Szafran Jennifer C , Woods Parker S , Meliton Angelo Y , Shamaa Obada R , Tian Yufeng , Mutlu Gökhan M. , Hamanaka Robert B.
Published: June 2024

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that fibroblast activation is supported by metabolic reprogramming, including the upregulation of thede novosynthesis of glycine, the most abundant amino acid found in collagen protein. How fibroblast metabolic reprogramming is regulated downstream of TGF-β is incompletely understood. We and others have shown that TGF-β-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote increased expression of the enzymes required forde novoglycine synthesis; however, whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored. Here, we used RNA sequencing to determine how both ATF4 and mTOR regulate gene expression in human lung fibroblasts following TGF-β. We found that ATF4 primarily regulates enzymes and transporters involved in amino acid homeostasis as well as aminoacyl-tRNA synthetases. mTOR inhibition resulted not only in the loss of ATF4 target gene expression, but also in the reduced expression of glycolytic enzymes and mitochondrial electron transport chain subunits. Analysis of TGF-β-induced changes in cellular metabolite levels confirmed that ATF4 regulates amino acid homeostasis in lung fibroblasts while mTOR also regulates glycolytic and TCA cycle metabolites. We further analyzed publicly available single cell RNAseq data sets and found increased expression of ATF4 and mTOR metabolic targets in pathologic fibroblast populations from the lungs of IPF patients. Our results provide insight into the mechanisms of metabolic reprogramming in lung fibroblasts and highlight novel ATF4 and mTOR-dependent pathways that may be targeted to inhibit fibrotic processes.
DCXknockout ferret reveals a neurogenic mechanism in cortical development
Authors: Wang Wei , Yin Chonghai , Wen Shaonan , Liu Zeyuan , Wang Bosong , Zeng Bo , Sun Le , Zhou Xin , Zhong Suijuan , Zhang Junjing , Ma Wenji , Wu Qian , Wang Xiaoqun
Published: June 2024

Doublecortin (DCX) is one of the major causal proteins leading to lissencephaly and subcortical band heterotopia in human patients. However, our understanding of this disease, as well as the function of DCX during neurogenesis, remains limited due to the absence of suitable animal models that accurately represent human phenotypes. Here, we conducted a comprehensive examination of the neocortex at different stages inDCXknockout ferrets. We corroborated the neurogenic functions ofDCXin progenitors. Loss of function of DCX led to the over-proliferation of neural progenitors and the truncation of basal processes of radial glial cells, which contributed to the thickening of cortices and the stalling of neurons underneath the cortical plate during neurogenic stages, respectively. We also present the first-ever cell atlas of the lissencephaly disease model, which embraces an almost reversed neuronal lamination distribution in the neocortex compared to the normal controls. Furthermore, we discovered alterations in molecular signatures tied to epilepsy, a condition frequently observed in lissencephaly patients. We also provided compelling evidence that the distribution of GABAergic inhibitory neurons in the cortex is intricately linked to glutamatergic excitatory neurons in a subtype-specific manner. In conclusion, our research offers new insights to expand our understanding of DCX’s functions and enrich our comprehension of lissencephaly’s intricacies.

Highlights

DCXferrets phenocopy human lissencephaly and subcortical band heterotopia syndrome

DCXis required for NPC proliferation and radial glial basal fiber extension

The atlas of lissencephalic cortex is illustrated using snRNA-seq and spatial transcriptome

Inhibitory neurons couple to excitatory neurons in a cell-type specific manner
Factors impacting Indian healthcare supply chain performance and influence in the public and private sector: the mediating role of blockchain technology adoption
Authors: Dhingra Sarthak , Raut Rakesh , Kumar Mukesh , Naik B. Koteswara Rao
Published: June 2024

Purpose

This study aims to identify several perspectives that affect the adoption of blockchain technology in India (BCTA) and evaluate their impact. To study the sector’s influence on adoption and the impact of BCTA on the performance of the Indian healthcare supply chain (HSCP) using BCTA as a mediating variable.

Design/methodology/approach

In this study, we first developed a conceptual model based on Organizational Information Processing Theory and Technology-Organization-Environment, then formulated hypotheses. Based on this, a questionnaire was developed, and data were gathered from experts in the Indian healthcare industry who were familiar with blockchain technology. AMOS 19 was used to analyze data using structural equation modelling.

Findings

All the factors have a significant positive influence on BCTA. Healthcare supply chain factors influenced the adoption most dominantly, followed by technological, environmental, organizational and record-keeping unit factors. Both the public and private sectors of HSCP benefited significantly from BCTA.

Practical implications

This research work is fruitful for healthcare practitioners, top management, academicians and policymakers in assessing BCTA’s impact on the HSCP.

Originality/value

We have attempted to evaluate the possible BCTA impact on HSCP. BCTA as a mediating variable and considering different perspectives for a holistic view of adoption in the Indian context add to this work’s originality.
Halal cosmetics repurchase intention: theory of consumption values perspective
Authors: Rachman Eva Syariefah , Amarullah Dudi
Published: June 2024

Purpose

By applying the theory of consumption value as a conceptual framework, this study aims to investigate the impact of consumption values, namely, functional value (FV), conditional value (CV), social value (SV), emotional value (EV) and epistemic value (EPV) on attitude and repurchase intention in the Halal cosmetics context.

Design/methodology/approach

Considering the increasing transmission cases of the new variant of COVID-19, online questionnaires were distributed to 233 Muslim consumers in Indonesia to collect data. The hypotheses were then validated using partial least square-structural equation modeling.

Findings

The results showed that FV, CV, SV, EV and EPV positively affect consumer attitudes toward Halal cosmetics. The attitude toward Halal cosmetics also positively affects Halal cosmetics repurchase intention.

Research limitations/implications

Two limitations are recognized for future studies, including the generalizability in consumer generation and the obscurity of what predictors determine consumer consumption values.

Practical implications

Halal cosmetics marketers must ensure that the positioning strategy and the value proposition contain elements of consumption values (functional, conditional, social, emotional and epistemic). In addition, an appropriate marketing communication strategy needs to be developed to strengthen consumer awareness and increase consumer knowledge regarding the values offered related to Halal cosmetics.

Originality/value

To the best of the authors’ knowledge, this study is the first attempt to comprehensively address the theory of consumption values by considering all consumption values to understand consumer repurchase intentions in the context of Halal cosmetics.