bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated network pharmacology and metabolomics to reveal the mechanism of Pinellia ternata inhibiting non-small cell lung cancer cells
Authors: Feng Fan , Hu Ping , Peng Lei , Xu Lisheng , Chen Jun , Chen Qiong , Zhang Xingtao , Tao Xingkui
Published: July 2024

Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds.
Healthcare workers’ views on decentralized primary health care management in Lesotho: a qualitative study
Authors: Birru Ermyas , Ndayizigiye Melino , Wanje George , Marole Tholoana , Smith Patrick D. , Koto Masebeo , McBain Ryan , Hirschhorn Lisa R. , Mokoena Mathabang , Michaelis Annie , Curtain Joel , Dally Emily , Andom Afom T. , Mukherjee Joia
Published: July 2024

Background

Lesotho experienced high rates of maternal (566/100,000 live births) and under-five mortality (72.9/1000 live births). A 2013 national assessment found centralized healthcare management in Ministry of Health led to fragmented, ineffective district health team management. Launched in 2014 through collaboration between the Ministry of Health and Partners In Health, Lesotho’s Primary Health Care Reform (LPHCR) aimed to improve service quality and quantity by decentralizing healthcare management to the district level. We conducted a qualitative study to explore health workers’ perceptions regarding the effectiveness of LPHCR in enhancing the primary health care system.

Methods

We conducted 21 semi-structured key informant interviews (KII) with healthcare workers and Ministry of Health officials purposively sampled from various levels of Lesotho’s health system, including the central Ministry of Health, district health management teams, health centers, and community health worker programs in four pilot districts of the LPHCR initiative. The World Health Organization’s health systems building blocks framework was used to guide data collection and analysis. Interviews assessed health care workers’ perspectives on the impact of the LPHCR initiative on the six-health system building blocks: service delivery, health information systems, access to essential medicines, health workforce, financing, and leadership/governance. Data were analyzed using directed content analysis.

Results

Participants described benefits of decentralization, including improved efficiency in service delivery, enhanced accountability and responsiveness, increased community participation, improved data availability, and better resource allocation. Participants highlighted how the reform resulted in more efficient procurement and distribution processes and increased recognition and status in part due to the empowerment of district health management teams. However, participants also identified limited decentralization of financial decision-making and encountered barriers to successful implementation, such as staff shortages, inadequate management of the village health worker program, and a lack of clear communication regarding autonomy in utilizing and mobilizing donor funds.

Conclusion

Our study findings indicate that the implementation of decentralized primary health care management in Lesotho was associated a positive impact on health system building blocks related to primary health care. However, it is crucial to address the implementation challenges identified by healthcare workers to optimize the benefits of decentralized healthcare management.
ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway
Authors: Ji Yang , Ni Chuangye , Shen Yanjun , Xu Zhenggang , Tang Lei , Yu Fei , Zhu Lingbang , Lu Hao , Zhang Chuanyong , Yang Shikun , Wang Xuehao
Published: July 2024

Background

Emerging evidence indicates the pivotal involvement of circular RNAs (circRNAs) in cancer initiation and progression. Understanding the functions and underlying mechanisms of circRNAs in tumor development holds promise for uncovering novel diagnostic indicators and therapeutic targets. In this study, our focus was to elucidate the function and regulatory mechanism of hsa-circ-0003764 in hepatocellular carcinoma (HCC).

Methods

A newly discovered hsa-circ-0003764 (circPTPN12) was identified from the circbase database. QRT-PCR analysis was utilized to assess the expression levels of hsa-circ-0003764 in both HCC tissues and cells. We conducted in vitro and in vivo experiments to examine the impact of circPTPN12 on the proliferation and apoptosis of HCC cells. Additionally, RNA-sequencing, RNA immunoprecipitation, biotin-coupled probe pull-down assays, and FISH were employed to confirm and establish the relationship between hsa-circ-0003764, PDLIM2, OTUD6B, P65, and ESRP1.

Results

In HCC, the downregulation of circPTPN12 was associated with an unfavorable prognosis. CircPTPN12 exhibited suppressive effects on the proliferation of HCC cells both in vitro and in vivo. Mechanistically, RNA sequencing assays unveiled the NF-κB signaling pathway as a targeted pathway of circPTPN12. Functionally, circPTPN12 was found to interact with the PDZ domain of PDLIM2, facilitating the ubiquitination of P65. Furthermore, circPTPN12 bolstered the assembly of the PDLIM2/OTUD6B complex by promoting the deubiquitination of PDLIM2. ESRP1 was identified to bind to pre-PTPN12, thereby fostering the generation of circPTPN12.

Conclusions

Collectively, our findings indicate the involvement of circPTPN12 in modulating PDLIM2 function, influencing HCC progression. The identified ESRP1/circPTPN12/PDLIM2/NF-κB axis shows promise as a novel therapeutic target in the context of HCC.

Graphical Abstract
Diagnosis, treatment and management of lipodystrophy: the physician perspective on the patient journey
Authors: Patni Nivedita , Chard Craig , Araújo-Vilar David , Phillips Helen , Magee David A. , Akinci Baris
Published: July 2024

Background

Lipodystrophy syndromes are a heterogeneous group of rare, life-limiting diseases characterized by a selective loss of adipose tissue and severe metabolic complications. There is a paucity of information describing the experiences and challenges faced by physicians who have seen and treated patients with lipodystrophy. This study aimed to provide a better understanding of the physician’s perspective regarding the patient journey in lipodystrophy, including diagnosis, the burden of disease, and treatment approaches.

Methods

Thirty-three physicians from six countries who had seen or treated patients with lipodystrophy were interviewed using a semi-structured questionnaire. Interviews were transcribed, anonymized, and analyzed for themes and trends. Four main themes were developed: (1) the diagnostic journey in lipodystrophy including the disease features or ‘triggers’ that result in the onward referral of patients to specialist medical centers with experience in managing lipodystrophy; (2) the impact of lipodystrophy on patient quality of life (QoL); (3) the use of standard therapies and leptin replacement therapy (metreleptin) in lipodystrophy, and (4) barriers to metreleptin use.

Results

Participants reported that, due to their rarity and phenotypic heterogeneity, lipodystrophy cases are frequently unrecognized, leading to delays in diagnosis and medical intervention. Early consultation with multidisciplinary specialist medical teams was recommended for suspected lipodystrophy cases. The development and progression of metabolic complications were identified as key triggers for the referral of patients to specialist centers for follow-up care. Participants emphasized the impact of lipodystrophy on patient QoL, including effects on mental health and self-image. Although participants routinely used standard medical therapies to treat specific metabolic complications associated with lipodystrophy, it was acknowledged that metreleptin was typically required in patients with congenital generalized lipodystrophy and in some acquired generalized and partial lipodystrophy cases. A lack of experience among some participants and restrictions to access remained as barriers to metreleptin use.

Conclusions

To our knowledge, this is one of the first studies describing the qualitative experiences of physicians regarding the diagnosis and management of lipodystrophy. Other physician-centered studies may help increase the awareness of lipodystrophy among the wider medical community and support clinical approaches to this rare disease.
Radiomics predict the WHO/ISUP nuclear grade and survival in clear cell renal cell carcinoma
Authors: Li Xiaoxia , Lin Jinglai , Qi Hongliang , Dai Chenchen , Guo Yi , Lin Dengqiang , Zhou Jianjun
Published: July 2024

Objectives

This study aimed to assess the predictive value of radiomics derived from intratumoral and peritumoral regions and to develop a radiomics nomogram to predict preoperative nuclear grade and overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC).

Methods

The study included 395 patients with ccRCC from our institution. The patients in Center A (anonymous) institution were randomly divided into a training cohort (n = 284) and an internal validation cohort (n = 71). An external validation cohort comprising 40 patients from Center B also was included. Computed tomography (CT) radiomics features were extracted from the internal area of the tumor (IAT) and IAT combined peritumoral areas of the tumor at 3 mm (PAT 3 mm) and 5 mm (PAT 5 mm). Independent predictors from both clinical and radiomics scores (Radscore) were used to construct a radiomics nomogram. Kaplan–Meier analysis with a log-rank test was performed to evaluate the correlation between factors and OS.

Results

The PAT 5-mm radiomics model (RM) exhibited exceptional predictive capability for grading, achieving an area under the curves of 0.80, 0.80, and 0.90 in the training, internal validation, and external validation cohorts. The nomogram and RM gained from the PAT 5-mm region were more clinically useful than the clinical model. The association between OS and predicted nuclear grade derived from the PAT 5-mm Radscore and the nomogram-predicted score was statistically significant (p < 0.05).

Conclusion

The CT-based radiomics and nomograms showed valuable predictive capabilities for the World Health Organization/International Society of Urological Pathology grade and OS in patients with ccRCC.

Critical relevance statement

The intratumoral and peritumoral radiomics are feasible and promising to predict nuclear grade and overall survival in patients with clear cell renal cell carcinoma, which can contribute to the development of personalized preoperative treatment strategies.

Key Points

The multi-regional radiomics features are associated with clear cell renal cell carcinoma (ccRCC) grading and prognosis.

The combination of intratumoral and peritumoral 5 mm regional features demonstrated superior predictive performance for grading.

The nomogram and radiomics models have a broad range of clinical applications.

Graphical Abstract
A double CYP27A1 gene mutation in spinal cerebrotendinous xanthomatosis in a patient presenting with spastic gait: a case report
Authors: Min Je Hong , Kim Yoon Seob , Son Myeong Jin , Joo In Soo
Published: July 2024

Background

Cerebrotendinous xanthomatosis (CTX, OMIM #213700) is a rare inherited metabolic disease caused by the mutation in the CYP27A1 gene. Spinal CTX is a rare clinical subgroup of CTX which lacks typical symptoms seen in classical CTX. Here we report a spinal CTX case revealed double mutation of CYP27A1 gene.

Case presentation

A 42-year-old Asian man visited our hospital with spastic gait started at 35. Physical examination showed bilateral masses on his Achilles tendons and were identified as xanthoma on ankle magnetic resonance imaging (MRI). Brain and spinal cord MRI revealed high signal lesions in bilateral cerebellar dentate nuclei and long tract lesions involving lateral corticospinal and gracile tracts. Gene analysis revealed double heterozygous mutation, c.223C > T (p. Gln75Ter) and c.1214G > A (p. Arg405Gln).

Conclusions

We believe that novel mutation detected in our case might have a role in the pathomechanism in CTX. Moreover, spinal CTX should be considered in the patients only presenting with pyramidal symptoms, as CTX shows good prognosis in early treatment with chenodeoxycholic acid.
Multi-user directional modulation with reconfigurable holographic surfaces
Authors: Yağan M. Yaser , Keşir Samed , Hökelek İbrahim , Pusane Ali E. , Görçin Ali
Published: July 2024

Large intelligent surfaces arise as an emerging technology and critical building block for sixth-generation (6G) wireless networks. Reconfigurable holographic surfaces (RHSs) have been attracting significant attention recently as active antenna arrays with the capability of forming narrow beams at low cost and complexity. This paper introduces the directional modulation (DM) concept for RHS, where a large number of elements are exploited to control not only the signal’s power at the receiver but also its phase. Thus, a novel DM algorithm is proposed for RHS enables modulating a carrier wave to transmit information toward specific directions while broadcasting arbitrary signals toward other directions. Error vector magnitude results are reported for multiple users, where the directions of two users with respect to the RHS are varied. Mutual information result is also provided for 6 users to demonstrate the application of RHS for the physical layer security. Results are highly promising for future low-cost and secure spatially multiplexed communications.
The relationship between Stroma AReactive Invasion Front Areas (SARIFA), Warburg-subtype and survival: results from a large prospective series of colorectal cancer patients
Authors: Offermans Kelly , Reitsam Nic G. , Simons Colinda C. J. M. , Grosser Bianca , Zimmermann Jessica , Grabsch Heike I. , Märkl Bruno , van den Brandt Piet A.
Published: July 2024

Background

Stroma AReactive Invasion Front Areas (SARIFA) is a recently identified haematoxylin & eosin (H&E)based histopathologic biomarker in gastrointestinal cancers, including colorectal cancer (CRC), defined as direct contact between tumour cells and adipocytes at the tumour invasion front. The current study aimed at validating the prognostic relevance of SARIFA in a large population-based CRC series as well as at investigating the relationship between SARIFA-status and previously established Warburg-subtypes, both surrogates of the metabolic state of the tumour cells.

Methods

SARIFA-status (positive versus negative) was determined on H&E slides of 1,727 CRC specimens. Warburg-subtype (high versus moderate versus low) data was available from our previous study. The associations between SARIFA-status, Warburg-subtype, clinicopathological characteristics and CRC-specific as well as overall survival were investigated.

Results

28.7% (n=496) CRC were SARIFA-positive. SARIFA-positivity was associated with more advanced disease stage, higher pT category, and more frequent lymph node involvement (all p<0.001). SARIFA-positivity was more common in Warburg-high CRC. 44.2% (n=219) of SARIFA-positive CRCs were Warburg-high compared to 22.8% (n=113) being Warburg-low and 33.1% (n=164) being Warburg-moderate (p<0.001). In multivariable-adjusted analysis, patients with SARIFA-positive CRCs had significantly poorer CRC-specific (HRCRC-specific 1.65; 95% CI 1.41-1.93) and overall survival (HRoverall survival 1.46; 95% CI 1.28-1.67) independent of clinically known risk factors and independent of Warburg-subtype. Combining the SARIFA-status and the Warburg-subtype to a combination score (SARIFA-negative/Warburg-high versus SARIFA-positive/Warburg-low versus SARIFA-positive/Warburg-high, and so on) did not improve the survival prediction compared to the use of SARIFA-status alone (SARIFA-negative + Warburg-high: HRCRC-specific 1.08; 95% CI 0.84-1.38; SARIFA-positive + Warburg-low: HRCRC-specific 1.79; 95% CI 1.32-2.41; SARIFA-positive + Warburg-high: HRCRC-specific 1.58; 95% CI 1.23-2.04).

Conclusions

Our current study is the by far largest external validation of SARIFA-positivity as a novel independent negative prognostic H&E-based biomarker in CRC. In addition, our study shows that SARIFA-positivity is associated with the Warburg-high subtype. Further research is warranted to provide a more mechanistic understanding of the underlying tumour biology. Based on our data, we conclude SARIFA-status should be implemented in pathologic routine practice to stratify CRC patients.
Surgical outcome of endoscopic endonasal approach as a modality of management for large and giant pituitary adenomas: a retrospective case series
Authors: Izz-alarab Shebl , Zohney Michael , Issa Saied A. , Abdelwahab Abdelaleem , Al-Abyad Ashraf G. , Aziz Mohamed M.
Published: July 2024

Background

Large and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed.

Patients and methods

The primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%).

Results

42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection.

Conclusions

Endoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures.
β-H-Spectrin is a key component of an apical-medial hub of proteins during cell wedging in tube morphogenesis
Authors: Gillard Ghislain , Röper Katja
Published: July 2024

Coordinated cell shape changes are a major driver of tissue morphogenesis, with apical constriction of epithelial cells leading to tissue bending. We previously identified that interplay between the apical-medial actomyosin, which drives apical constriction, and the underlying longitudinal microtubule array has a key role during tube budding of salivary glands in the Drosophila embryo. At this microtubule–actomyosin interface, a hub of proteins accumulates, and we have shown before that this hub includes the microtubule–actin crosslinker Shot and the microtubule minus-end-binding protein Patronin. Here, we identify two actin-crosslinkers, β-heavy (H)-Spectrin (also known as Karst) and Filamin (also known as Cheerio), and the multi-PDZ-domain protein Big bang as components of the protein hub. We show that tissue-specific degradation of β-H-Spectrin leads to reduction of apical-medial F-actin, Shot, Patronin and Big bang, as well as concomitant defects in apical constriction, but that residual Patronin is still sufficient to assist microtubule reorganisation. We find that, unlike Patronin and Shot, neither β-H-Spectrin nor Big bang require microtubules for their localisation. β-H-Spectrin is instead recruited via binding to apical-medial phosphoinositides, and overexpression of the C-terminal pleckstrin homology domain-containing region of β-H-Spectrin (β-H-33) displaces endogenous β-H-Spectrin and leads to strong morphogenetic defects. This protein hub therefore requires the synergy and coincidence of membrane- and microtubule-associated components for its assembly and function in sustaining apical constriction during tubulogenesis.
Consistent changes in muscle phenotype and mitochondrial abundance underlie dive performance across multiple lineages of diving ducks
Authors: Schell Elizabeth R. , Scott Graham R. , Dawson Neal J. , Winker Kevin , McCracken Kevin G.
Published: July 2024

Diving animals must sustain high muscle activity with finite oxygen (O2) to forage underwater. Studies have shown that some diving mammals exhibit changes in the metabolic phenotype of locomotory muscles compared with non-divers, but the pervasiveness of such changes across diving animals is unclear, particularly among diving birds. Here, we examined whether changes in muscle phenotype and mitochondrial abundance are associated with dive capacity across 17 species of ducks from three distinct evolutionary clades (tribes) in the subfamily Anatinae: the longest diving sea ducks, the mid-tier diving pochards and the non-diving dabblers. In the gastrocnemius (the primary swimming and diving muscle), mitochondrial volume density in both oxidative and glycolytic fiber types was 70% and 30% higher in sea ducks compared with dabblers, respectively. These differences were associated with preferential proliferation of the subsarcolemmal subfraction, the mitochondria adjacent to the cell membrane and nearest to capillaries, relative to the intermyofibrillar subfraction. Capillary density and capillary-to-fiber ratio were positively correlated with mitochondrial volume density, with no variation in the density of oxidative fiber types across tribes. In the pectoralis, sea ducks had greater abundance of oxidative fiber types than dabblers, whereas pochards were intermediate between the two. These data suggest that skeletal muscles of sea ducks have a heightened capacity for aerobic metabolism and an enhanced ability to utilize O2 stores in the blood and muscle while diving.
TitrationAnalysis: a tool for high throughput binding kinetics data analysis for multiple label-free platforms
Authors: Li Kan , Huntwork Richard H.C. , Horn Gillian Q. , Alam S. Munir , Tomaras Georgia D. , Dennison S. Moses
Published: July 2024

Label-free techniques including Surface Plasmon Resonance (SPR) and Biolayer Interferometry (BLI) are biophysical tools widely used to collect binding kinetics data of bimolecular interactions. To efficiently analyze SPR and BLI binding kinetics data, we have built a new high throughput analysis tool named the TitrationAnalysis. It can be used as a package in the Mathematica scripting environment and ultilize the non-linear curve-fitting module of Mathematica for its core function. This tool can fit the binding time course data and estimate association and dissociation rate constants (ka and kd respectively) for determining apparent dissociation constant (KD ) values. The high throughput fitting process is automatic, requires minimal knowledge on Mathematica scripting and can be applied to data from multiple label-free platforms. We demonstrate that the TitrationAnalysis is optimal to analyze antibody-antigen binding data acquired on Biacore T200 (SPR), Carterra LSA (SPR imaging) and ForteBio Octet Red384 (BLI) platforms. The ka , kd and KD values derived using TitrationAnalysis very closely matched the results from the commercial analysis software provided specifically for these instruments. Additionally, the TitrationAnalysis tool generates user-directed customizable results output that can be readily used in downstream Data Quality Control associated with Good Clinical Laboratory Practice operations. With the versatility in source of data input source and options of analysis result output, the TitrationAnalysis high throughput analysis tool offers investigators a powerful alternative in biomolecular interaction characterization.
Stakeholder Interviews to Inform Best Practice for Public Facing COVID-19 Wastewater Dashboards
Authors: Morales Daniela , Rhodes Tim , O'Reilly Kathleen M
Published: July 2024

Background Wastewater (WW) -based epidemiology is the detection of pathogens from wastewater, typically sewage systems. Its use gained popularity during the COVID-19 pandemic as a rapid and non-invasive way to assess infection prevalence in a population. Public facing dashboards for SARS-CoV-2 were developed in response to the discovery that RNA biomarkers were being shed in faeces before symptoms. However, there is not a standard template or guidance for countries to follow. The aim of this research is to reflect on how currently available dashboards evolved during the pandemic and identify suitable content and rationale from these experiences. Methods Interviews were carried out with implementers and users of dashboards for SARS-CoV-2 WW data across Europe and North America. The interviews addressed commonalities and inconsistencies in displaying epidemiological data of SARS-CoV-2, clinical parameters of COVID-19, data on variants, and data transparency. Results The thematic analysis identified WW dashboard elements that can facilitate standardization, or at least interoperability. These elements emphasise communication among developers under the same organization, open access for identified stakeholders, and data summarized with a time-intensive graphic analysis through normalizing at least by population. Simultaneous communication of clinical surveillance is recommended. More research is needed on flow and faecal indicators for normalization of WW data, and on the analysis and representation of variants. Discussion WW dashboard development between 2020-2023 provided a ‘real-time’ iterative process of data representation, and several recommendations have been identified. Communication of data through dashboards has the potential to support early warning systems for infectious diseases.
Guideline recommendations on the role of the general practitioner in the diagnosis of dementia: a protocol for a scoping review of clinical practice guidelines
Authors: Cronin Mary , Jennings Aisling , Perry Marieke , Hartigan Irene , O'Dowd Séan , Cornally Nicola , Timmons Suzanne , Walsh Kieran , Foley Tony
Published: July 2024

Introduction A timely diagnosis of dementia offers the opportunity of earlier intervention and activation of coordinated care plans. General Practitioners (GPs) play a key role in dementia diagnosis, from symptom recognition to clinical assessment, investigation, diagnosis and onward referral for confirmation of the diagnosis and subtyping. Dementia clinical practice guidelines (CPGs) offer clinicians guidance on dementia care but often do not specifically address the role of the GP in the diagnostic process. This protocol outlines a scoping review to identify evidence-based dementia clinical practice guidelines and map the recommended role of GPs in the diagnosis of dementia. Method The scoping review will be conducted using the Arksey and O'Malley framework, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) will be used to guide the reporting. We will search five electronic databases (PubMed, CINAHL, Embase, PsycINFO, Cochrane Library) for dementia CPGs published since 2019. CPGs are often not published in peer-reviewed journals; therefore, a parallel search of relevant grey literature will be conducted. We will also search the websites of GP professional organisations and guideline developers. Two reviewers will independently screen all articles based on inclusion criteria, with conflicts resolved by a third reviewer. Conclusion This scoping review will examine up-to-date dementia CPGs to determine recommendations for the role of GPs in the assessment, investigation, diagnosis and onward referral of patients with suspected dementia to secondary care.
Medical students' perspective on the United States Medical Licensing Examination (USMLE) Step 1 transition to Pass/Fail
Authors: Prasad Samiksha , Perez Christine , Carnevale Kate J.F.
Published: July 2024

Background The transition of the United States Medical Licensing Exam: Step 1 to Pass/Fail (P/F), from scored, caused uncertainty about students’ preparedness and wellbeing related to the exam. Comparison of study behavior and results, before and after the P/F transition can provide insights for the medical curriculum and student support. The aim of this study is to evaluate students’ perceptions of their efforts in Step 1 preparation, as compared to cohort performances to determine the impact of the transition of Step 1 to P/F on medical students. Methods Data from four cohorts of second-year medical students (Class of 2022–25, N = 204) were collected from their dedicated Step 1 self-study block. Student study regiments, aggregate practice test results, Step 1 pass rates and post-block self-reported surveys were analyzed qualitatively to compare student effort and outcomes for scores and P/F cohorts. Results Analysis of practice exam averages across the four student cohorts demonstrates a potentially slower and less rigorous start to Step 1 self-studying during the dedicated preparation block for the cohorts that took the P/F Step 1 exam format as compared to the previous cohorts that prepared for a scored Step 1 exam. Similarly, self-reported study regiments decreased in the median number of hours/day and number of weeks of study for the cohorts with P/F Step 1 exam. There was also a slight shift in the type of study resources used, between the two groups, with the scored group using more traditional board preparation resources. Conclusions The P/F transition of the Step 1 exam may lead to reduced student preparedness and may require adjustments in the resources and support provided by institutions.
Triple P Model: Revitalizing Peer Feedback with Key Stakeholders Engagement
Authors: Asghari Shabnam , Sohrabi Tayebeh , Bethune Cheri , Graham Wendy , Tobin Alexandria Jennifer
Published: July 2024

Introduction Peer feedback is crucial for enhancing learners' competency and skills in achieving educational goals. Despite its proven impact on learning outcomes, learners often lack the necessary skills and confidence to engage in meaningful peer feedback. Objective Our primary aim was to create a practical and memorable feedback model that considers all key individuals involved in educational feedback processes. Method We utilized a narrative case study within the 6for6 program, a research skills development initiative for rural physicians. Employing the nominal group technique, the 6for6 core team held regular meetings to address challenges in peer feedback processes and craft a practical and memorable model. Result The developed peer-feedback model focuses on three key persons: presenters, peers, and pedagogues (Triple P). Each person has an associated rubric and a simple acronym for ease of recall. Additionally, a learning plan template was adapted to help learners organize their thoughts and progress toward their goals. Conclusion Recognizing feedback as an interactive and multi-faceted process, our model, created within the 6for6 program, encompasses main persons and has the potential to enhance learning opportunities and outcomes. While initially designed for rural physician research skills development, this model is adaptable to various educational settings and contexts.
Teaching of reflection in higher education: a narrative review
Authors: Phenwan Tharin
Published: July 2024

Background Healthcare professional students (HCPs) are encouraged to utilise reflection during and after their study programmes as a part of their life-long learning skill and professional competencies. However, the way in which the concept of reflection is taught and its’ influence students’ capacity to reflect have not been fully explored. This narrative review aimed to explore how the concept of reflection is taught in higher education and how the teaching of reflection influences HCP students’ capacity to reflect. Methods Articles that were published during 2014–2024 within three databases, PubMed, CINAHL and ERIC were searched. 1929 articles were eligible for screening. 93 articles were further assessed for eligibility. Results 18 articles were included. The included articles were geographically well-distributed in both the Global North and Global South countries, indicating universal interest in the topic. Eight articles had qualitative study designs; six had quantitative designs and four had mixed-method designs. Conceptually, the teaching of reflection could be categorised as a spectrum, ranging from: i) structured format (reflective templates or debriefing); ii) semi-structured format (physical/virtual small group discussions, video recordings, AI generative arts, in-verse reflection and concept mapping) and iii) flexible and creative (art-based pedagogy or narratives). All included articles indicated students actual and perceived better understanding of reflection. This claim is supported both quantitatively and qualitatively via either validated instruments or narratives and themes based on students’ textual outputs. Conclusions This review identified several teaching methods that help facilitating students’ capacity to reflect. Findings are unable to recommend the most efficient way to teach reflection since it depends on students’ progress in their programmes. However, a more relational approach to teaching of reflection is recommended. Students might begin their reflective journey with a structured format of teaching of reflection then gradually move to less-rigid format of the teaching to empower students’ autonomy.
Rethinking GLAMs as commons: a conceptual framework
Authors: Avdikos Vasilis , Dragouni Mina , Michailidou Martha , Pettas Dimitris
Published: July 2024

In this paper, we reflect on ‘new commons’ theory and elaborate on the ontology of memory institutions with the aim to develop a comprehensive conceptual framework for ‘commons-oriented’ GLAMs (Galleries, Libraries, Archives and Museums). In doing so, we propose an alternative for governing and managing cultural heritage against a backdrop of limited public funding and pressures for developing memory institutions into more inclusive, participatory and ‘entrepreneurial’ organisations. Our theoretical analysis is grounded in the review of the extant literature, including both the ‘Ostromian’ and ‘Autonomist’ schools of thought, drawing particularly on the new commons (urban, digital, cultural/heritage commons) to inform our framework. The conceptual schema we present here is adapted to fit with the idiosyncrasies of the sector, describing the functioning of commoning practices in GLAMs. Such a framework is critical for navigating future research and devising workable solutions to address current challenges for memory institutions in Europe.
Practical guidelines for Bayesian phylogenetic inference using Markov Chain Monte Carlo (MCMC)
Authors: Barido-Sottani Joëlle , Schwery Orlando , Warnock Rachel C. M. , Zhang Chi , Wright April Marie
Published: July 2024

Phylogenetic estimation is, and has always been, a complex endeavor. Estimating a phylogenetic tree involves evaluating many possible solutions and possible evolutionary histories that could explain a set of observed data, typically by using a model of evolution. Modern statistical methods involve not just the estimation of a tree, but also solutions to more complex models involving fossil record information and other data sources. Markov Chain Monte Carlo (MCMC) is a leading method for approximating the posterior distribution of parameters in a mathematical model. It is deployed in all Bayesian phylogenetic tree estimation software. While many researchers use MCMC in phylogenetic analyses, interpreting results and diagnosing problems with MCMC remain vexing issues to many biologists. In this manuscript, we will offer an overview of how MCMC is used in Bayesian phylogenetic inference, with a particular emphasis on complex hierarchical models, such as the fossilized birth-death (FBD) model. We will discuss strategies to diagnose common MCMC problems and troubleshoot difficult analyses, in particular convergence issues. We will show how the study design, the choice of models and priors, but also technical features of the inference tools themselves can all be adjusted to obtain the best results. Finally, we will also discuss the unique challenges created by the incorporation of fossil information in phylogenetic inference, and present tips to address them.
Advancements in integrated robotic sensing: A European perspective
Authors: Mineo Carmelo
Published: July 2024

Robotic Non-destructive Testing and Sensing stands at the forefront of technological innovation, offering capabilities in assessing structural integrity, safety, and material quality across diverse industries. This comprehensive review article provides a detailed exploration of the field, focusing on the substantial contributions of European researchers and institutions. The need for non-destructive testing has been a constant in industries that rely on structural integrity, including aerospace, manufacturing, energy, construction, and healthcare. Traditional testing methods, such as radiography, ultrasonic testing, magnetic particle testing, and dye penetrant testing, have been integral for quality control and safety assurance. However, the robotisation of such methods has marked a profound shift, enabling precise, fast, efficient, and repeatable testing while minimising human exposure to hazardous environments. European researchers and institutions have played an instrumental role in driving the evolution of integrated robotic sensing. The historical perspective of the field reveals the pioneering spirit of Europe, as collaborative initiatives led to the development of robotic platforms equipped with advanced sensors and testing techniques. A critical aspect of the European impact on robotic inspection applications lies in developing advanced sensors, innovative robotic platforms, novel robotic path-planning and control approaches and data collection and visualisation tools. These developments continue to influence the global landscape of robotic sensing. European researchers remain at the forefront of current trends and innovations as the field continues to evolve. This review article will delve into these recent advancements, highlighting Europe’s pivotal role in pushing the boundaries of technology and application. The implications and applications of robotic sensing reverberate across multiple sectors worldwide. From inspecting critical aerospace components to ensuring the quality of manufactured goods, these technologies underpin safety and quality standards.
The associations between religious/spiritual beliefs and behaviours and study participation in a prospective cohort study (ALSPAC) in Southwest England
Authors: Morgan Jimmy , Halstead Isaac , Northstone Kate , Major-Smith Daniel
Published: July 2024

Background Longitudinal studies are key to understanding risk factors for health, well-being, and disease, yet associations may be biased if study invitation and participation are non-random. Religious/spiritual beliefs and behaviours (RSBB) are increasingly recognised as having potentially important relationships with health. However, it is unclear whether RSBB is associated with study participation. We examine whether RSBB is associated with participation in the longitudinal birth cohort ALSPAC (Avon Longitudinal Study of Parents and Children). Methods Three RSBB factors were used: religious belief (belief in God/a divine power; yes/not sure/no), religious affiliation (Christian/none/other), and religious attendance (frequency of attendance at a place of worship). Participation was measured in three ways: i) total number of questionnaires/clinics completed (linear and ordinal models); ii) completion of the most recent questionnaire (logistic model); and iii) length of participation (survival model). Analyses were repeated for the ALSPAC mothers, their partners, and the study children, and were adjusted for relevant socio-demographic confounders. Results Religious attendance was positively associated with participation in all adjusted models in all three cohorts. For example, study mothers who attended a place of worship at least once a month on average completed two more questionnaires (out of a possible 50), had 50% greater odds of having completed the most recent questionnaire, and had 25% reduced risk of drop-out, relative to those who did not attend. In the adjusted analyses, religious belief and attendance were not associated with participation. However, the majority of unadjusted models showed associations between RSBB and participation. Conclusion After adjusting for confounders, religious attendance – not religious belief or affiliation – was associated with participation in ALSPAC. These results indicate that use of RSBB variables (and religious attendance in particular) may result in selection bias and spurious associations; these potential biases should be explored and discussed in future studies using these data.
The genome sequence of the Figure of Eighty moth Tethea ocularis Linnaeus, 1767
Authors: Boyes Douglas , Wawman Denise C. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: July 2024

We present a genome assembly from an individual male Tethea ocularis (the Figure of Eighty; Arthropoda; Insecta; Lepidoptera; Drepanidae). The genome sequence is 339.1 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.28 kilobases in length
testCompareR: an R package to compare two binary diagnostic tests using paired data
Authors: Wilson Kyle J. , Roldán-Nofuentes José A. , Henrion Marc Y.R.
Published: July 2024

Background Binary diagnostic tests are commonly used in medicine to answer a question about a patient’s clinical status, most commonly, do they or do they not have some disease. Recent advances in statistical methodologies for performing inferential statistics to compare commonly used test metrics for two diagnostic tests have not yet been implemented in a robust statistical package. Methods Up-to-date statistical methods to compare the test metrics achieved by two binary diagnostic tests are implemented in the new R package testCompareR. The output and efficiency of testCompareR is compared to the only other available package which performs this function, DTComPair, using a motivating example. Results testCompareR achieves similar results to DTComPair using statistical methods with improved coverage and asymptotic performance. Further, testCompareR is faster than the currently available package and requires fewer pre-processing steps in order to produce accurate results. Conclusions testCompareR provides a new tool to compare the test metrics for two binary diagnostic tests compared with the gold standard. This tool allows flexible inputs, which minimises the need for data pre-processing, and operates in very few steps, so that it is easy to use even for those less experienced with R. testCompareR achieves results comparable to those computed by DTComPair, using optimised statistical methods and with improved computational efficiency.
Home-based depression care for older people delivered by lay providers in Nigeria: protocol for a proof-of-concept cluster randomised controlled trial using an age adapted electronic mental health gap action programme intervention guide app for mobile devices
Authors: Ojagbemi Akin , Mediavilla Roberto , Daley Stephanie , Oyedapo-Ishola Hephzibah , Olojugba Toyin , Olowoyo Caroline , Feeney Yvonne , Ayuso-Mateos Jose Luis , Gureje Oye
Published: July 2024

Background We conducted iterative adaptation of the generic e-version (2.0) of the WHO Mental Health Gap Action Programme Intervention Guide (emhGAP-IG) to overcome the challenges in detection and home-based management of depression in older people by frontline non-specialist Primary Health Care (PHC) workers. Objectives In this study, we will assess early implementation outcomes (feasibility, appropriateness, and acceptability) and evaluate parameters and procedures to inform a larger trial of the age adapted emhGAP-IG (emhGAP-Age) for home-based management of depression in older people. Methods A cluster Randomised Controlled Trial (cRCT) will be conducted in Ibadan, Nigeria. A minimum of 10 PHC clinics will be randomized to have their staff trained in emhGAP-Age (k=5 PHC clinics) or the emhGAP-IG (k=5 PHC clinics). PHC clinics will be the unit of clustering. Two PHC workers will be recruited per clinic (n=10 PHC workers per arm). They will receive training on a version of intervention relevant to their clinic. PHC workers in the intervention cluster will home-deliver emhGAP-Age to 55 depressed persons who are 60 years or older. 55 depressed older participants in the control clusters will receive clinic-based treatment using the emhGAP-IG (Usual care within PHC clinics in Nigeria). The primary outcome will be postintervention difference in Patient Health Questionnaire (PHQ-9) total scores at 6 months follow-up. Conclusions Home delivery of an age adapted emhGAP-IG has the potential to bridge existing gaps in continuity of care between PHC services and community-based care for depression and other priority mental health conditions in older people. Registration ClinicalTrials.gov (NCT06125899; 08/11/2023).