bluuebunny/crossref_metadata_2025 huggingface dataset:
How patients experience respect in healthcare: findings from a qualitative study among multicultural women living with HIV
Authors: Fernandez Sofia B. , Ahmad Alya , Beach Mary Catherine , Ward Melissa K. , Jean-Gilles Michele , Ibañez Gladys , Ladner Robert , Trepka Mary Jo
Published: March 2024

Background

Respect is essential to providing high quality healthcare, particularly for groups that are historically marginalized and stigmatized. While ethical principles taught to health professionals focus on patient autonomy as the object of respect for persons, limited studies explore patients’ views of respect. The purpose of this study was to explore the perspectives of a multiculturally diverse group of low-income women living with HIV (WLH) regarding their experience of respect from their medical physicians.

Methods

We analyzed 57 semi-structured interviews conducted at HIV case management sites in South Florida as part of a larger qualitative study that explored practices facilitating retention and adherence in care. Women were eligible to participate if they identified as African American (n = 28), Hispanic/Latina (n = 22), or Haitian (n = 7). They were asked to describe instances when they were treated with respect by their medical physicians. Interviews were conducted by a fluent research interviewer in either English, Spanish, or Haitian Creole, depending on participant’s language preference. Transcripts were translated, back-translated and reviewed in entirety for any statements or comments about “respect.” After independent coding by 3 investigators, we used a consensual thematic analysis approach to determine themes.

Results

Results from this study grouped into two overarching classifications: respect manifested in physicians’ orientation towards the patient (i.e., interpersonal behaviors in interactions) and respect in medical professionalism (i.e., clinic procedures and practices). Four main themes emerged regarding respect in provider’s orientation towards the patient: being treated as a person, treated as an equal, treated without blame or prejudice, and treated with concern/emotional support. Two main themes emerged regarding respect as evidenced in medical professionalism: physician availability and considerations of privacy.

Conclusions

Findings suggest a more robust conception of what ‘respect for persons’ entails in medical ethics for a diverse group of low-income women living with HIV. Findings have implications for broadening areas of focus of future bioethics education, training, and research to include components of interpersonal relationship development, communication, and clinic procedures. We suggest these areas of training may increase respectful medical care experiences and potentially serve to influence persistent and known social and structural determinants of health through provider interactions and health care delivery.
Nursing students’ attitudes toward intimate partner violence and its relationship with self-esteem and self-efficacy
Authors: El-Etreby Rania Rabie , Hamed Warda Elshahat , AbdElhay Eman Sameh , Kamel Nesma Ahmed
Published: March 2024

Understanding nursing students’ attitudes toward Intimate Partner Violence (IPV) is pivotal because it may impact the care and support, they provide victims. This study aimed to explore nursing students’ attitudes toward intimate partner violence and its relationship with self-esteem and self-efficacy. A cross-sectional descriptive research design was used in the current study in the faculty of nursing at Mansoura University, Egypt. A total of 1322 nursing students participated in the study. Data were collected from April to June 2023 by using various tools: sociodemographic interviews and academic data profiles, the Intimate Partner Violence Attitude Scale (IPVAS)—Revised, the Rosenberg Self-Esteem Scale (RSE) (Arabic version), and the General Self-Efficacy Scale. Results: The findings show the distribution of the Intimate Partner Violence Attitude Scale (IPVAS), with 78.7% of nursing students disapproving of the abuse domain, 72.6% (approving of the violence domain) and 34.2% approving of the control domain. 65.8% had a moderate level of self-esteem, and 62.8% had a low level of self-efficacy. The study concluded that self-esteem and self-efficacy are significant in shaping attitudes toward intimate partner violence; higher levels of self-esteem and self-efficacy are associated with lower approval for intimate partner violence. Further research is needed to explore the factors that contribute to attitudes and levels of self-esteem and self-efficacy among nursing students. It would also be useful to study how education and training affect these attitudes.
Reasons for implementation success despite health system constraints: qualitative insights on ‘what worked’ for cotrimoxazole preventive therapy
Authors: Müller Pia , Mabasso Edna , Lapão Luís Velez , Sidat Mohsin
Published: March 2024

Background

Although Cotrimoxazole preventive therapy (CPT) has shown to be highly efficacious in reducing morbidity and mortality among people living with Human immunodeficiency virus (HIV) under ‘ideal world’ study conditions, operational challenges are limiting its effectiveness when implementing in countries most affected by the HIV epidemic. The fact that Mozambican authorities reported high coverage of CPT among patients with HIV, has led to this qualitative case study aimed at exploring possible factors responsible for the successful implementation of CPT in the Province of Maputo.

Methods

Between February and April 2019, we individually interviewed nine governmental stakeholders, including the person responsible for the HIV Program, the person responsible for the TB Program and the person responsible for Pharmaceutical management at three administrative levels (central, provincial and district level). Interviews were recorded, transcribed, and analysed thematically using MAXQDA Analytics Pro. Findings were translated from Portuguese into English.

Results

Five themes iteratively emerged: (a) Role of governance & leadership, (b) Pharmaceutical strategies, (c) Service delivery modifications, (d) Health care provider factors, and (e) Patients’ perspectives.

Interviews revealed that continuous supply of cotrimoxazole (CTZ) had been facilitated through multiple-source procurement and a push-pull strategy. One part of CTZ arrived in kits that were imported from overseas and distributed to public health facilities based on their number of outpatient consultations (push strategy). Another part of CTZ was locally produced and distributed as per health facility demand (pull strategy). Strong district level accountability also contributed to the public availability of CTZ. Interviewees praised models of differentiated care, the integrated HIV service delivery and drug delivery strategies for reducing long queues at the health facility, better accommodating patients’ needs and reducing their financial and organisational burden.

Conclusions

This study presents aspects that governmental experts believed to be key for the implementation of CPT in the Province of Maputo, Mozambique. Enhancing the implementation outcomes – drug availability and feasibility of the health facility-based service delivery – seemed crucial for the implementation progress. Reasons for the remarkable patient acceptability of CPT in our study setting should be further investigated.
Implementing routine paediatric height/length and weight screening and weight management advice by clinicians: an evaluation
Authors: Krstic Slavica , Dennis Sarah , Southcombe Faye , Denney-Wilson Elizabeth
Published: March 2024

Objective

To determine the views of health care professionals (HCPs) in South Western Sydney Local Health District (SWSLHD) about the effectiveness of implementation strategies used to increase routine height/length and weight screening, advice, and referral for children and adolescents. A secondary aim was to explore the prevalence of weight bias among HCPs.

Methods

A questionnaire was sent to all HCPs who had undertaken online or face-to-face training between December 2018 and June 2020 in SWSLHD (n=840). The questionnaire collected data on their experience of routine height and weight screening and the effectiveness of strategies used in the implementation. It also included a weight bias assessment. Data were provided by the New South Wales (NSW) Ministry of Health on the performance of routine height/length and weight measures entered into the electronic medical records (eMR) in SWSLHD.

Results

Of the 840 questionnaires sent, 87 were undeliverable; of the remaining 753, 285 were returned (38% response rate). More than half (53%, 151/285) of the participants were nurses. Most HCPs agreed that there was a need for routine screening and reported that education, training, and access to resources were the most helpful implementation strategies. Most HCPs were confident in performing routine screening but were less confident in raising the issue of weight with children and their families. Barriers to implementation were lack of time, equipment, appropriate clinical setting, and HCPs’ perceptions and beliefs about obesity.

Conclusion

Routine screening is the first step in identifying children and adolescents at risk of overweight and obesity, but many HCP found it challenging to incorporate into daily practice. Multifaceted strategies are effective in increasing routine screening across diverse healthcare settings so that children and adolescents receive timely and appropriate intervention.
Acceptance and expectations of healthcare workers and community during the COVID-19 vaccine rollout in Bhavnagar city, western India: a qualitative exploration
Authors: Makwana Mohit N. , Shekhda Hiren J. , Rupani Mihir P.
Published: March 2024

Background

COVID-19 vaccine was launched in India on January 16, 2021. There is a paucity of robust evidence from qualitative studies on the acceptability and expectations of potential recipients from the COVID-19 vaccine around the time of its rollout in India. We conducted this study to explore the acceptance and expectations of the COVID-19 vaccine among the healthcare workers and community in Bhavnagar, India.

Methods

During January 2021, in-depth interviews were conducted with potential vaccine recipients in Bhavnagar city—health care workers, people over the age of 50, and people of any age with comorbidities. A total of 28 in-depth interviews were performed, including 16 healthcare workers and 12 community beneficiaries. An in-depth interview guide was developed based on the constructs of the health belief model. Following written informed consent from all participants, all interviews were audio-recorded, transcribed in English and codes were generated using thematic analysis. Qualitative qualifiers were used due describe our study findings.

Results

Most of healthcare workers and a majority of people from the community have shown willingness to be vaccinated with COVID-19 vaccine as they had trust on the results of the clinical trials and on the government. Some participants showed hesitancy, which was attributed to concerns regarding safety and efficacy, negative news reports in the media and lack of awareness regarding benefits of vaccine. Some healthcare workers were hesitant due to a lack of transparency in sharing the results of clinical trials. Very few showed refusal in getting vaccinated due to their belief that they won’t be infected with SARS-CoV-2 virus as they might have developed immunity against it. Most of the participants expected good efficacy, minimal/no side effects, rapid and wide coverage of vaccine and a perception of getting back to pre-COVID life sooner.

Conclusions

Most of the potential recipients were willing to take the COVID-19 vaccine around the time of its initial roll out. Future vaccine rollout campaigns could reduce refusals by timely demand generation activities on vaccine safety/efficacy, involving leaders/influencers, addressing grievances, and minimizing misinformation.
Comparing the clinical practice and prescribing safety of locum and permanent doctors: observational study of primary care consultations in England
Authors: Grigoroglou Christos , Walshe Kieran , Kontopantelis Evangelos , Ferguson Jane , Stringer Gemma , Ashcroft Darren M. , Allen Thomas
Published: March 2024

Background

Temporary doctors, known as locums, are a key component of the medical workforce in the NHS but evidence on differences in quality and safety between locum and permanent doctors is limited. We aimed to examine differences in the clinical practice, and prescribing safety for locum and permanent doctors working in primary care in England.

Methods

We accessed electronic health care records (EHRs) for 3.5 million patients from the CPRD GOLD database with linkage to Hospital Episode Statistics from 1st April 2010 to 31st March 2022. We used multi-level mixed effects logistic regression to compare consultations with locum and permanent GPs for several patient outcomes including general practice revisits; prescribing of antibiotics; strong opioids; hypnotics; A&E visits; emergency hospital admissions; admissions for ambulatory care sensitive conditions; test ordering; referrals; and prescribing safety indicators while controlling for patient and practice characteristics.

Results

Consultations with locum GPs were 22% more likely to involve a prescription for an antibiotic (OR = 1.22 (1.21 to 1.22)), 8% more likely to involve a prescription for a strong opioid (OR = 1.08 (1.06 to 1.09)), 4% more likely to be followed by an A&E visit on the same day (OR = 1.04 (1.01 to 1.08)) and 5% more likely to be followed by an A&E visit within 1 to 7 days (OR = 1.05 (1.02 to 1.08)). Consultations with a locum were 12% less likely to lead to a practice revisit within 7 days (OR = 0.88 (0.87 to 0.88)), 4% less likely to involve a prescription for a hypnotic (OR = 0.96 (0.94 to 0.98)), 15% less likely to involve a referral (OR = 0.85 (0.84 to 0.86)) and 19% less likely to involve a test (OR = 0.81 (0.80 to 0.82)). We found no evidence that emergency admissions, ACSC admissions and eight out of the eleven prescribing safety indicators were different if patients were seen by a locum or a permanent GP.

Conclusions

Despite existing concerns, the clinical practice and performance of locum GPs did not appear to be systematically different from that of permanent GPs. The practice and performance of both locum and permanent GPs is likely shaped by the organisational setting and systems within which they work.
An investigation into how accurately UK rabbit owners identify pain in their pet rabbits
Authors: Forder Charlotte , Benato Livia , Rooney Nicola J.
Published: March 2024

Background

Rabbits are popular family pets. They are prey species and so have evolved to hide signs of illness and pain. Recent research has developed robust pain scales for use in a clinical setting, but to date none has examined rabbit owners’ ability to recognise pain in their animals. This study investigated how owners identify pain in their pet rabbits and their ability to correctly identify different levels of pain, in order to determine any need for owner education in this area.

Methods

Owners were recruited via Facebook and a two-part online survey was distributed. Part one collected data on demographics, owners’ knowledge of pain signs and beliefs about pain in rabbits. Part two asked respondents to pain score eight videos of rabbits in different levels of pain for comparison to pain scores made by three experts. We used a simplified version of the Bristol Rabbit Pain Score (BRPS) which involved a single 0 to 3 scale. We explored the number of pain signs each respondent could list, the total score given to the videos, and their deviation from the experts’ scores.

Results

A total of 500 respondents completed part one of the survey and 345 additionally completed Part two. Respondents were on average able to state five signs of pain (range 0–12), but females stated significantly more (p = 0.018), as did those who worked with rabbits (p = 0.004) and those with experience of their rabbit having an operation (p = 0.01). Overall, 98.6% of respondents thought rabbits felt pain as much or more that dogs and cats. In Part two, respondents more frequently agreed with the experts when identifying rabbits in no pain (88.8%) and severe pain (65.2%), but there was lower agreement when identifying mild (28.4%) and moderate pain (43.2%). Respondents overall rated pain lower than experts with an average total pain score of 11.9 compared to 18 given by the experts.

Conclusions

Most rabbit owners are able to list numerous pain signs and are generally able to identify pain-free rabbits and those in severe pain. Owners’ ability to differentiate between mild and moderate pain is more limited and could benefit from training in the subtler signs of pain. Veterinary professionals are well placed to educate owners about signs of pain in rabbits and should be aware of areas where owners’ knowledge can be improved.
A systematic review: is Anopheles vagus a species complex?
Authors: Dalilah Dalilah , Syafruddin Din , Saleh Irsan , Ghiffari Ahmad , Vernadesly Leo , Syahrani Lepa , Irdayanti Irdayanti , Anwar Chairil
Published: March 2024

Background

Anopheles vagus (subgenus Cellia) has been identified as a vector for malaria, filariasis, and Japanese encephalitis in Asia. Sporozoites of Plasmodium falciparum and Plasmodium vivax have been found in this zoophilic mosquito in Asia and Indonesia. This study systematically reviews publications regarding An. vagus species, variation, bio-ecology, and malaria transmission in various localities in Asia, especially Indonesia, to determine whether the current data support An. vagus as a species complex.

Methods

The databases Pubmed, Scopus, Europe PMC, and Proquest were searched to identify information regarding the morphology, karyotypes, polytene chromosome, cross-mating, ecology, and molecular identification of An. vagus was then evaluated to determine whether there were possible species complexes.

Results

Of the 1326 articles identified, 15 studies were considered for synthesis. The Anopheles spp. samples for this study came from Asia. Eleven studies used morphology to identify An. vagus, with singular studies using each of karyotype identification, chromosomal polytene identification, and cross-breeding experiments. Ten studies used molecular techniques to identify Anopheles spp., including An. vagus. Most studies discovered morphological variations of An. vagus either in the same or different areas and ecological settings. In this review, the members of An. vagus sensu lato grouped based on morphology (An. vagus, An. vagus vagus, An. vagus limosus, and An. limosus), karyotyping (form A and B), and molecular (An. vagus genotype A and B, An. vagus AN4 and AN5). Genetic analysis revealed a high conservation of the ITS2 fragment among members except for the An. vagus genotype B, which was, in fact, Anopheles sundaicus. This review also identified that An. vagus limosus and An. vagus vagus were nearly identical to the ITS2 sequence.

Conclusion

Literature review studies revealed that An. vagus is conspecific despite the distinct morphological characteristic of An. vagus and An. limosus. Further information using another barcoding tool, such as mitochondrial COI and ND6 and experimental cross-mating between the An. vagus and An. limosus may provide additional evidence for the status of An. vagus as a species complex.
Human periodontal ligament stem cell sheets activated by graphene oxide quantum dots repair periodontal bone defects by promoting mitochondrial dynamics dependent osteogenic differentiation
Authors: An Na , Yan Xiaoyuan , Qiu Qiujing , Zhang Zeying , Zhang Xiyue , Zheng Bowen , Zhao Zhenjin , Guo Jiajie , Liu Yi
Published: March 2024

Background

Bone defects in the maxillofacial region restrict the integrity of dental function, posing challenges in clinical treatment. Bone tissue engineering (BTE) with stem cell implants is an effective method. Nanobiomaterials can effectively enhance the resistance of implanted stem cells to the harsh microenvironment of bone defect areas by promoting cell differentiation. Graphene oxide quantum dots (GOQDs) are zero-dimensional nanoscale derivatives of graphene oxide with excellent biological activity. In the present study, we aimed to explore the effects of GOQDs prepared by two methods (Y-GOQDs and B-GOQDs) on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), as well as the effect of gelatin methacryloyl (GelMA)-encapsulated GOQD-induced hPDLSC sheets on the repair of mandibular periodontal defects in rats. We also explored the molecular biological mechanism through which GOQD promotes bone differentiation.

Results

There were significant differences in oxygen-containing functional groups, particle size and morphology between Y-GOQDs and B-GOQDs. Y-GOQDs promoted the osteogenic differentiation of hPDLSCs more effectively than did B-GOQDs. In addition, GelMA hydrogel-encapsulated Y-GOQD-induced hPDLSC cell sheet fragments not only exhibited good growth and osteogenic differentiation in vitro but also promoted the repair of mandibular periodontal bone defects in vivo. Furthermore, the greater effectiveness of Y-GOQDs than B-GOQDs in promoting osteogenic differentiation is due to the regulation of hPDLSC mitochondrial dynamics, namely, the promotion of fusion and inhibition of fission.

Conclusions

Overall, Y-GOQDs are more effective than B-GOQDs at promoting the osteogenic differentiation of hPDLSCs by regulating mitochondrial dynamics, which ultimately contributes to bone regeneration via the aid of the GelMA hydrogels in vivo.

Graphical Abstract
Choosing and accessing COVID-19 treatment options: a qualitative study with patients, caregivers, and health care providers in Lebanon
Authors: Hoteit Reem , Hassoun Aya , Bou Sanayeh Elie , Saade Marie Christelle , Honein-AbouHaidar Gladys , Akl Elie A.
Published: March 2024

Background

The coronavirus disease 2019 (COVID-19) pandemic has strained healthcare systems globally, particularly in terms of access to medicines. Lebanon has been greatly affected by the pandemic, having faced concomitant financial and economic crises. The objective of the study was to understand the experiences of patients with COVID-19 in Lebanon, as well as those of their families, and healthcare providers, with regards to their treatment decisions and accessibility to COVID-19 medicines.

Methods

For this qualitative study, we conducted 28 semi-structured interviews. We used purposive sampling to recruit participants with a diverse range of perspectives. The data collection phase spanned from August to November 2021 and was conducted virtually. After transcribing and translating the interviews, we employed thematic analysis to identify recurring themes and patterns.

Results

In total, 28 individuals participated in this study. Participants highlighted challenges owing to the COVID-19 pandemic and economic crisis. Accessing COVID-19 medicines posed major hurdles for physicians and patients, given limited availability, global shortages, local circumstances, community hoarding and stockpiling by pharmacies. Providers based treatment decisions on research, local and international practice guidelines, experiences and expert feedback. Patients sought information from social media, community members and physicians, as well as through word of mouth. Accessing medicines involved navigating the healthcare system, the black market, charities, personal networks and political parties and sourcing from abroad. The medicines were either free, subsidized or at inflated costs.

Conclusions

This study highlights the diversity and complexity of factors influencing decision-making and accessing medicines during the COVID-19 pandemic in Lebanon. Future research should explore strategies for ensuring medicine access during crises, drawing insights from comparative studies across different countries.
Polyploidy and mTOR signaling: a possible molecular link
Authors: Choudhury Debopriya , Ghosh Dhruba , Mondal Meghna , Singha Didhiti , Pothuraju Ramesh , Malakar Pushkar
Published: March 2024

Polyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body’s development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy.
Changes in lipid metabolism track with the progression of neurofibrillary pathology in tauopathies
Authors: Olešová Dominika , Dobešová Dana , Majerová Petra , Brumarová Radana , Kvasnička Aleš , Kouřil Štěpán , Stevens Eva , Hanes Jozef , Fialová Ľubica , Michalicová Alena , Piešťanský Juraj , Šinský Jakub , Kaňovský Petr , Friedecký David , Kováč Andrej
Published: March 2024

Background

Accumulation of tau leads to neuroinflammation and neuronal cell death in tauopathies, including Alzheimer’s disease. As the disease progresses, there is a decline in brain energy metabolism. However, the role of tau protein in regulating lipid metabolism remains less characterized and poorly understood.

Methods

We used a transgenic rat model for tauopathy to reveal metabolic alterations induced by neurofibrillary pathology. Transgenic rats express a tau fragment truncated at the N- and C-terminals. For phenotypic profiling, we performed targeted metabolomic and lipidomic analysis of brain tissue, CSF, and plasma, based on the LC-MS platform. To monitor disease progression, we employed samples from transgenic and control rats aged 4, 6, 8, 10, 12, and 14 months. To study neuron-glia interplay in lipidome changes induced by pathological tau we used well well-established multicomponent cell model system. Univariate and multivariate statistical approaches were used for data evaluation.

Results

We showed that tau has an important role in the deregulation of lipid metabolism. In the lipidomic study, pathological tau was associated with higher production of lipids participating in protein fibrillization, membrane reorganization, and inflammation. Interestingly, significant changes have been found in the early stages of tauopathy before the formation of high-molecular-weight tau aggregates and neurofibrillary pathology. Increased secretion of pathological tau protein in vivo and in vitro induced upregulated production of phospholipids and sphingolipids and accumulation of lipid droplets in microglia. We also found that this process depended on the amount of extracellular tau. During the later stages of tauopathy, we found a connection between the transition of tau into an insoluble fraction and changes in brain metabolism.

Conclusion

Our results revealed that lipid metabolism is significantly affected during different stages of tau pathology. Thus, our results demonstrate that the dysregulation of lipid composition by pathological tau disrupts the microenvironment, further contributing to the propagation of pathology.
Liver-specific adiponectin gene therapy suppresses microglial NLRP3-inflammasome activation for treating Alzheimer’s disease
Authors: Ng Roy Chun-Laam , Jian Min , Ma Oscar Ka-Fai , Xiang Ariya Weiman , Bunting Myriam , Kwan Jason Shing-Cheong , Wong Curtis Wai-Kin , Yick Leung-Wah , Chung Sookja Kim , Lam Karen Siu-Ling , Alexander Ian E. , Xu Aimin , Chan Koon-Ho
Published: March 2024

Adiponectin (APN) is an adipokine which predominantly expresses in adipocytes with neuroprotective and anti-inflammatory effects. We have recently indicated that circulatory trimeric APN can enter the brain by crossing the blood–brain barrier (BBB) and modulate microglia-mediated neuroinflammation. Here, we found that the microglial NLR family pyrin domain containing 3 (NLRP3)-inflammasome activation was exacerbated in APN−/−5xFAD mice in age-dependent manner. The focus of this study was to develop a new and tractable therapeutic approach for treating Alzheimer’s disease (AD)-related pathology in 5xFAD mice using peripheral APN gene therapy. We have generated and transduced adeno-associated virus (AAV2/8) expressing the mouse mutated APN gene (APNC39S) into the liver of 5xFAD mice that generated only low-molecular-weight trimeric APN (APNTri). Single dose of AAV2/8-APNC39S in the liver increased circulatory and cerebral APN levels indicating the overexpressed APNTri was able to cross the BBB. Overexpression of APNTri decreased both the soluble and fibrillar Aβ in the brains of 5xFAD mice. AAV2/8-APNTri treatment reduced Aβ-induced IL-1β and IL-18 secretion by suppressing microglial NLRP3-inflammasome activation. The memory functions improved significantly in AAV-APNTri-treated 5xFAD mice with reduction of dystrophic neurites. These findings demonstrate that peripheral gene delivery to overexpress trimeric APN can be a potential therapy for AD.

Graphical Abstract
SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression
Authors: Hussein Hosni A. M. , Thabet Ali A. , Wardany Ahmed A. , El-Adly Ahmed M. , Ali Mohamed , Hassan Mohamed E. A. , Abdeldayem Mohamed A. B. , Mohamed Abdul-Rahman M. A. , Sobhy Ali , El-Mokhtar Mohamed A. , Afifi Magdy M. , Fathy Samah M. , Sultan Serageldeen
Published: March 2024

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.
Concurrent KRAS p.G12C mutation and ANK3::RET fusion in a patient with metastatic colorectal cancer: a case report
Authors: Bedau Tillmann , Heydt Carina , Siebolts Udo , Zander Thomas , Kraemer Max , Loeser Heike , Buettner Reinhard , Quaas Alexander
Published: March 2024

Background

Colorectal cancer (CRC) frequently involves mutations in the KRAS gene, impacting therapeutic strategies and prognosis. The occurrence of KRAS mutations typically precludes the presence of RET fusions, with current medical literature suggesting a mutual exclusivity between these two genetic alterations. We present a unique case that challenges this notion.

Case Presentation

An 85-year-old female with metastatic CRC was found to have a combination of genetic anomalies that is to the best of our knowledge not yet described in the medical literature: a KRAS p.G12C mutation, associated with oncogenesis and treatment resistance, and an ANK3::RET fusion, an infrequent but targetable mutation in CRC. This molecular profile was uncovered through comprehensive genomic sequencing after the patient experienced metachronous tumor dissemination. The presence of both genetic events complicates the treatment approach.

Conclusions

The identification of both a KRAS p.G12C mutation and an ANK3::RET fusion in the same CRC patient adds a new layer to the oncogenic landscape and treatment considerations for CRC. It highlights the intricate decision-making required in the era of precision medicine, where targeted therapies must be carefully chosen and potentially combined to combat complex genetic profiles. The case emphasizes the urgency of investigating the clinical effects of concurrent or sequential use of KRAS p.G12C and RET inhibitors to inform future therapeutic guidelines and improve patient outcomes in similar cases.
Identification of SARS-CoV-2-specific T cell and its receptor
Authors: Zhang Qian , Liang Qing , Zhang Rui , Wang Nan , Xiao Xu , Shao Jiahao , Wang Kejia
Published: March 2024

The T-cell receptor (TCR) repertoires exhibits distinct signatures associated with COVID-19 severity. However, the precise identification of vaccine-induced SARS-CoV-2-specific TCRs and T-cell immunity mechanisms are unknown. We developed a machine-learning model that can differentiate COVID-19 patients from healthy individuals based on TCR sequence features with an accuracy of 95.7%. Additionally, we identified SARS-CoV-2-specific T cells and TCR in HLA-A*02 vaccinated individuals by peptide stimulation. The SARS-CoV-2-specific T cells exhibited higher cytotoxicity and prolonged survival when targeting spike-pulsed cells in vitro or in vivo. The top-performing TCR was further tested for its affinity and cytotoxic effect against SARS-CoV-2-associated epitopes. Furthermore, single-cell RNA sequencing (scRNA-seq), immune repertoire sequencing (IR-seq) and flow cytometry were used to access vaccine-induced cellular immunity, which demonstrated that robust T cell responses (T cell activation, tissue-resident memory T cell (Trm) generation, and TCR clonal expansion) could be induced by intranasal vaccination. In summary, we identified the SARS-CoV-2-associated TCR repertoires profile, specific TCRs and T cell responses. This study provides a theoretical basis for developing effective immunization strategies.
CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells
Authors: Zhang Qingsong , Zhang Rong , Li Yuzhi , Yang Xiaojun
Published: March 2024

Background

The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated.

Results

The bioinformatics data revealed a negative correlation between the patient’s survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-β1/Smad2/3 signaling pathway activation.

Conclusions

CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.
Can artificial intelligence detect type 2 diabetes in women by evaluating the pectoral muscle on tomosynthesis: diagnostic study
Authors: Yashar Meltem M. , Izci Ilayda Begum , Gungoren Fatma Zeynep , Eren Abdulkadir A. , Mert Ali A. , Durur-Subasi Irmak I.
Published: March 2024

Objectives

This retrospective single-center analysis aimed to evaluate whether artificial intelligence can detect type 2 diabetes mellitus by evaluating the pectoral muscle on digital breast tomosynthesis (DBT).

Material method

An analysis of 11,594 DBT images of 287 consecutive female patients (mean age 60, range 40–77 years) was conducted using convolutional neural networks (EfficientNetB5). The inclusion criterion was left-sided screening images with unsuspicious interpretation who also had a current glycosylated hemoglobin A1c (HBA1c) % value. The exclusion criteria were inadequate imaging, history of breast cancer, and/or diabetes mellitus. HbA1c values between 5.6 and 6.4% were categorized as prediabetic, and those with values ≥ 6.5% were categorized as diabetic. A recorded HbA1c ≤ 5.5% served as the control group. Each group was divided into 3 subgroups according to age. Images were subjected to pattern analysis parameters then cropped and resized in a format to contain only pectoral muscle. The dataset was split into 85% for training and 15% for testing the model’s performance. The accuracy rate and F1-score were selected as performance indicators.

Results

The training process was concluded in the 15th epoch, each comprising 1000 steps, with an accuracy rate of 92% and a loss of only 0.22. The average specificity and sensitivity for all 3 groups were 95%. The F1-score was 0.95. AUC-ROC was 0.995. PPV was 94%, and NPV was 98%.

Conclusion

Our study presented a pioneering approach, applying deep learning for the detection of diabetes mellitus status in women using pectoral muscle images and was found to function with an accuracy rate of 92%.

Critical relevance statement

AI can differentiate pathological changes within pectoral muscle tissue by assessing radiological images and maybe a potential diagnostic tool for detecting diabetes mellitus and other diseases that affect muscle tissues.

Key points

• AI may have an opportunistic use as a screening exam for diabetes during digital breast tomosynthesis.

• This technique allows for early and non-invasive detection of diabetes mellitus by AI.

• AI may have broad applications in detecting pathological changes within muscle tissue.

Graphical Abstract
Association of lower extremity peripheral arterial disease with quantitative muscle features from computed tomography angiography
Authors: Hu Ge , Chen Yuexin , Mu Chunlin , Zhang Xinyue , Wang Yun , Wang Yining , Xue Huadan , Zhang Daming , Jin Zhengyu
Published: March 2024

Objectives

To explore the association between lower extremity muscle features from CTA and peripheral arterial disease (PAD) severity using digital subtraction angiography (DSA) as reference standard.

Methods

Informed consent was waived for this Institutional Review Board approved retrospective study. PAD patients were recruited from July 2016 to September 2020. Two radiologists evaluated PAD severity on DSA and CTA using runoff score. The patients were divided into two groups: mild PAD (DSA score ≤ 7) vs. severe PAD (DSA score > 7). After segmenting lower extremity muscles from CTA, 95 features were extracted for univariable analysis, logistic regression model (LRM) analysis, and sub-dataset analysis (PAD prediction based on only part of the images). AUC of CTA score and LRMs for PAD prediction were calculated. Features were analyzed using Student’sttest and chi-squared test.p < 0.05 was considered statistically significant.

Results

A total of 56 patients (69 ± 11 years; 38 men) with 56 lower legs were enrolled in this study. The lower leg muscles of mild PAD group (36 patients) showed higher CT values (44.6 vs. 39.5,p < 0.001) with smaller dispersion (35.6 vs. 41.0,p < 0.001) than the severe group (20 patients). The AUC of CTA score, LRM-I (constructed with muscle features), and LRM-II (constructed with muscle features and CTA score) for PAD severity prediction were 0.81, 0.84, and 0.89, respectively. The highest predictive performance was observed in the image subset of the middle and inferior segments of lower extremity (LRM-I, 0.83; LRM-II, 0.90).

Conclusions

Lower extremity muscle features are associated with PAD severity and can be used for PAD prediction.

Critical relevance statement

Quantitative image features of lower extremity muscles are associated with the degree of lower leg arterial stenosis/occlusion and can be a beneficial supplement to the current imaging methods of vascular stenosis evaluation for the prediction of peripheral arterial disease severity.

Key points

• Compared with severe PAD, lower leg muscles of mild PAD showed higher CT values (39.5 vs. 44.6, p < 0.001).

• Models developed with muscle CT features had AUC = 0.89 for predicting PAD.

• PAD severity prediction can be realized through the middle and inferior segment of images (AUC = 0.90).

Graphical Abstract
Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials
Authors: Muzi Mark , Peterson Lanell M. , Specht Jennifer M. , Hippe Daniel S. , Novakova-Jiresova Alena , Lee Jean H. , Kurland Brenda F. , Mankoff David A. , Obuchowski Nancy , Linden Hannah M. , Kinahan Paul E.
Published: March 2024

Background

Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients that have bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.

Methods

For this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified by the most commonly used PET parameter, the maximum tumor voxel normalized by dose and body weight (SUVmax) and also by the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals for SUVmax and SULpeak were used to determine the limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment.

Results

The mean relative difference of SUVmax and SULpeak in 38 bone tumors of the first cohort were 4.3% and 6.7%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and − 16.3% for SUVmax, and 21.2% and − 17.5% for SULpeak. 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification using SULpeak for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria for SULpeak changed the status of 3 patients compared to the standard Positron Emission Tomography Response Criteria in Solid Tumors of ± 30% SULpeak.

Conclusion

In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG SUVmax, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions in these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.
Improving monitoring and management methods is of the utmost importance in countries at risk of invasion by the pinewood nematode
Authors: Robinet Christelle , Raffin Annie , Jactel Hervé , Kersaudy Emmanuel , Deuffic Philippe , Clopeau Armand , Hotte Hoël , Kleinhentz Marc , Robin Cécile , Roux Géraldine , Villate Laure , Castagnone-Sereno Philippe
Published: March 2024

Key message

The invasive pine wood nematode is a major threat to pine forests worldwide, causing extensive tree mortality. Although scientific knowledge and control measures are continuously improving, important gaps remain. We argue that some key questions, notably related to early detection and pest management, need to be urgently tackled in countries at risk of invasion such as France.
Positive solutions for the Riemann–Liouville-type fractional differential equation system with infinite-point boundary conditions on infinite intervals
Authors: Yu Yang , Ge Qi
Published: March 2024

In this paper, we study the existence and uniqueness of positive solutions for a class of a fractional differential equation system of Riemann–Liouville type on infinite intervals with infinite-point boundary conditions. First, the higher-order equation is reduced to the lower-order equation, and then it is transformed into the equivalent integral equation. Secondly, we obtain the existence and uniqueness of positive solutions for each fixed parameter $\lambda >0$
λ
>
0
by using the mixed monotone operators fixed-point theorem. The results obtained in this paper show that the unique positive solution has good properties: continuity, monotonicity, iteration, and approximation. Finally, an example is given to demonstrate the application of our main results.