bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient experience of discharge opioid analgesia and care provision following spine surgery: A mixed methods study
Authors: Allen Megan L , Pastor Adam , Leslie Kate , Fitzpatrick Brennan , Hogg Malcolm , Lau Hui , Manski-Nankervis Jo-Anne
Published: February 2025

Background

Perioperative opioid stewardship programs are increasingly being introduced to guide responsible use around the time of surgery to reduce opioid-related harm to patients. However, patient experiences of perioperative opioid stewardship programs are underexplored.

Methods

We designed a mixed methods study to explore patients’ experiences of perioperative opioid stewardship in the post-operative period following spine surgery. We performed evaluative action research, combining quality improvement and ethnographic methodologies. Our quantitative methods were retrospective medical record review and targeted survey research. Our qualitative methods were online focus groups. The quantitative data were analysed using descriptive statistics, chi-square, and rank sum testing. The focus group data underwent inductive thematic analysis.

Results

Our spine surgery cohort for the four-month study period included 101 patients. The median total discharge opioid dispensed was 75 mg [interquartile range 75–150 mg], with 30% of patients prescribed modified release opioids on discharge. A subset of patients ( N = 14) participated in the online focus groups. The key themes that emerged from these sessions were (1) Supportive care delivery and rescue mechanisms were universally important to patient participants, providing great reassurance during their recovery; (2) Participants commonly believed opioid analgesia had an important role in recovery following spine surgery. Some patients were keen to dispose of surplus opioids whilst others intended to retain them; (3) Opioid analgesia access was variable, but established community prescriber relationships were important for post-discharge opioid re-prescription, and (4) The key future improvement suggestions included routine post-discharge contact and enhanced communication options back to the hospital if needed.

Discussion and conclusions

Our mixed methods approach provided rich insights into the pain and opioid analgesia experiences of patients following spine surgery. These insights are useful when seeking to optimise perioperative opioid stewardship programs including better meeting the needs of patient consumers. Limitations included potential response and selection bias for the online focus groups towards younger, higher socioeconomic status patients.
Clinical characteristics and outcome of non-cystic fibrosis bronchiectasis in children: A tertiary care perspective
Authors: Sitthikarnkha Phanthila , Anekvorakul Apichaya , Niamsanit Sirapoom , Techasatian Leelawadee , Saengnipanthkul Suchaorn , Uppala Rattapon
Published: February 2025

Introduction:

Bronchiectasis is a chronic respiratory disease caused by various respiratory and systemic conditions. It is now considered a potentially reversible disease, particularly when diagnosed early and managed with appropriate respiratory care strategies. Although rare in children, it typically develops in patients with recurrent lower respiratory tract infections. The etiology of bronchiectasis in children differs from that in adults. This study aims to identify the clinical features, causes, and outcomes of non-cystic fibrosis bronchiectasis in children at a tertiary center.

Methods:

A retrospective review was conducted among children with non-cystic fibrosis bronchiectasis who attended a university-affiliated hospital between January 2007 and December 2021. Clinical outcomes were assessed based on pulmonary function tests, exacerbation, and mortality.

Results:

The study included 35 children with non-cystic fibrosis bronchiectasis. The median age at diagnosis was 36 months (IQR: 24–170 months). Bronchiectasis was linked to underlying conditions in 22 cases (62.9%), such as primary immunodeficiency, chronic aspiration, and primary ciliary dyskinesia. Thirteen children had infectious-associated bronchiectasis (37.1%), with four cases related to pulmonary tuberculosis. At diagnosis, cystic bronchiectasis was most common ( n = 17, 48.6%), followed by varicose ( n = 13, 37.1%) and cylindrical bronchiectasis ( n = 5, 14.3%). Pulmonary exacerbation occurred in 28 (80%) children, with a higher rate in noninfectious bronchiectasis than postinfectious bronchiectasis (90.9% vs 61.5%, p = 0.036). Hospitalization was required for 26 (77.1%) children, with a higher rate of noninfectious bronchiectasis than postinfectious bronchiectasis (86.3% vs 53.8%, p = 0.033).

Conclusions:

Primary immune deficiency and chronic aspiration are the most common non-infective causes of non-cystic fibrosis bronchiectasis. Noninfectious bronchiectasis leads to higher exacerbation and hospitalization rates.
Reason Profiles for not Returning to Preinjury Activity Level Following Anterior Cruciate Ligament Reconstruction— A Latent Class Analysis With Subgroup Comparison of Patient-Reported Outcome Measures
Authors: Lamplot Joseph D. , Petushek Erich J. , Petit Camryn B. , Warren Shayla M. , Barber Foss Kim D. , Slutsky-Ganesh Alexis B. , Valencia Melanie , Kenyon Charles D , McPherson April L. , Xerogeanes John W. , Myer Gregory D. , Diekfuss Jed A.
Published: February 2025

Background:

Given the high proportion of athletes who do not return to sports (RTS) after anterior cruciate ligament reconstruction (ACLR), strategies are needed to identify at-risk patients and optimize rehabilitation for successful RTS after ACLR.

Purpose/Hypothesis:

This study used latent class analysis (LCA) to characterize a unique clustering of reasons why athletes do not return to their preinjury activity level after ACLR. We hypothesized that patients with high pain scores and high levels of fear would be less likely to return to their preinjury activity level.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

All patients at a single institution who underwent primary ACLR between 2005 and 2021 were contacted to complete a survey via REDCap. Patients’ ability to RTS and their preinjury activity level, reasons for inability to return to the preinjury activity level, and patient-reported outcome scores were collected from 981 patients. LCA was performed to identify and compare patterns among patients’ reasons for not returning to the preinjury activity level.

Results:

Of the 981 patients included, only 446 (45.5%) were fully able to return to their preinjury activity level. LCA categorized patients into 3 groups based on their reasons for not returning to preinjury activity levels: a high-function group (75.5%), which reported no barriers; a multisymptom group (16.1%), which cited pain, lack of strength, and instability; and a fear-limited group (8.4%), which reported fear as the sole reason. Among the high-function group, 86.2% reported RTS compared with <36.7% in the other classes. There was no difference in Knee injury and Osteoarthritis Outcome Score (KOOS) subscales—including Pain, Symptoms, or Activities of Daily Living—between the high-function and fear-limited groups; however, the multisymptom group presented with the lowest scores in all KOOS subscales ( P < .001). In addition, patient characteristics, the time from the index ACLR to the follow-up, and subsequent revision ACLR were similar between groups; however, the multisymptom profile demonstrated the highest proportion of allograft ACLR ( P = .04) and secondary ipsilateral surgery ( P < .001). Overall subjective knee grade (1-100) and Marx scores were highest in the high-function group, followed by fear-limited and multisymptom groups ( P < .001).

Conclusion:

Patients were differentiated into 3 distinct classes after primary ACLR. Furthermore, those with patient-reported characteristics of pain, lack of strength, instability, or fear were significantly less likely to return to their preinjury activity level or sport.
The Swift Rise and Sudden Fall: Examining the Collapse of Silicon Valley Bank
Authors: Jha Pratiksha , Akhtar Shakeb , Rana Prabha
Published: February 2025

The present case study is based on the recent collapse of Silicon Valley Bank (SVB), a respected bank known for its strong focus on financing start-ups and venture capital firms. The objective is to provide an account of the events that led to the collapse of SVB. The reasons for the collapse are manifolds; including a liquidity crisis triggered by a significant bank run on its deposits by start-up clients, macro-economic factors such as inflation surge and interest rate hikes, Dodd-Frank Act Amendment 2018, corporate governance and risk management issues. The sudden collapse had significant implications for start-up financing, with many start-ups facing a liquidity crisis and some shutting down altogether. The case is analysed with data extracted from SVB financial statements and the Bloomberg database. The findings reveal that Asset liability mismatch, regularity loopholes, aggressive decision-making, specific client concentration and financial market changes are the major reasons for bank failures. The case also provides some important lessons, including the importance of diversification, monitoring financial health, and building strong relationships with the customer base. The subject that this case will fit in is financial statement analysis, corporate finance and auditing.
Development and validation of a diagnostic prediction model for heart failure-related pleural effusions: the BANCA score
Authors: Porcel José M. , Trujillano Javier , Porcel Laura , Esquerda Aureli , Bielsa Silvia
Published: February 2025

Background

Heart failure (HF) is a common cause of pleural effusion (PE); however, its diagnosis can be challenging owing to overlapping clinical features with other causes. Measuring NT-proBNP levels is diagnostically useful, but the optimal cut-off point must be determined. This study aimed to optimize NT-proBNP cutoffs for diagnosing HF-related PEs and develop a scoring model to improve diagnostic precision.

Methods

A retrospective analysis was conducted on 2005 patients with PEs, who were divided into derivation and validation cohorts. ROC curve analysis identified the optimal cutoff point for NT-proBNP in pleural fluid and serum. A scoring system was developed based on logistic regression (TRIPOD statement) that included both clinical and laboratory variables. Its diagnostic accuracy was compared with that of existing methods using the area under the curve (AUC).

Results

NT-proBNP≥2500 pg·mL−1was found to be the optimal cut-off for identifying HF-related effusions. Pleural fluid NT-proBNP levels tended to have superior diagnostic accuracy compared to serum NT-proBNP levels. A scoring system, denominated as BANCA, for Bilateral effusions on chest radiographs, Age, NT-proBNP levels in pleural fluid, Cholesterol in pleural fluid, and Albumin gradient, demonstrated an AUC of 0.957, outperforming existing diagnostic criteria for identifying cardiac effusions. In cases misclassified as exudates by Light's criteria, the BANCA score accurately identified 80% of the HF-related PEs.

Conclusions

The BANCA score is a reliable tool for diagnosing HF-related PEs, offering superior accuracy compared to conventional methods. It is particularly useful for identifying cardiac effusions that are misclassified using traditional criteria.
Ramadan fasting for patients with chronic respiratory diseases: a systematic review and consensus recommendations for healthcare professionals
Authors: Khan F , Toor S , Abdulqawi R , Adamali H , Chalmers J , Chaudhuri N , Ghouri N , Jenkins RG , Murphy A , Rahman N , Rashid R , Satia I , Siddiqui S , Waqar S
Published: February 2025

Background

Ramadan, observed by nearly two billion Muslims worldwide, involves fasting from dawn to sunset, which can present challenges for individuals with chronic respiratory diseases due to altered medication regimens and oral intake restrictions. This study aimed to synthesise current evidence and develop consensus recommendations for managing asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and bronchiectasis during Ramadan.

Methods

A comprehensive search of electronic databases including MEDLINE, EMBASE, and Google Scholar was conducted following a pre-specified protocol (PROSPERO CRD42024532759) to identify studies on Ramadan fasting outcomes in individuals with chronic respiratory diseases. The findings informed consensus recommendations stratified by the risk of adverse outcomes using IDF-DAR risk assessment criteria. An international expert group of medical and religious experts refined these guidelines, achieving consensus approval.

Results

Eleven studies met the inclusion criteria, primarily addressing asthma and COPD, with no relevant studies on ILD or bronchiectasis. The studies indicated that fasting did not significantly impact hospitalisation rates or lung function tests in individuals with stable asthma and COPD. However, small sample sizes and methodological limitations restricted generalizability. Nineteen recommendations were developed to support patients considering fasting, emphasising pre-Ramadan consultations, individualised risk assessments, and medication regimens adjustments.

Conclusion

This systematic review highlights the need for larger, well-designed studies to understand Ramadan fasting implications across chronic respiratory diseases. The developed recommendations provide a structured approach to assess fasting risks, ensuring informed and safe guidance during Ramadan. Future research should address identified gaps, supporting evidence-based guidelines that reconcile medical and religious considerations.
Retraction Note: Accuracy of Genomic prediction for fleece traits in Inner Mongolia Cashmere goats
Authors: Yan Xiaochun , Li Jinquan , He Libing , Chen Oljibilig , Wang Na , Wang Shuai , Wang Xiuyan , Wang Zhiying , Su Rui
Published: February 2025

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12864-024-10249-7.
Measles in Canada: modelling outbreaks with variable vaccine coverage and interventions
Authors: McNichol Jennifer , Valizadeh Javad , Chaudhury Samara , Colijn Caroline
Published: February 2025

Background

The global incidence of measles has increased markedly since 2023. In Canada, where measles has had elimination status for more than two decades, most cases can typically be traced to travel. While the majority of Canadians are vaccinated against the measles virus, or considered immune due to previous infection, there are communities with low vaccination coverage.

Methods

In this study, we develop a stochastic Susceptible-Exposed-Infectious-Recovered model to explore what measles outbreaks could look like upon importation into Canada under a number of scenarios, vaccination coverage levels, and public health interventions. We collect reports of real-world measles outbreaks and compare them to our model outbreaks’ size and duration.

Results

Our model suggests that community level outbreaks can be controlled at or above 85% vaccination coverage with public health interventions and that above 95% coverage, 99% of measles introductions do not result in an outbreak. Below 85% coverage, outbreaks in small communities (size 1000) with relatively strong public health measures range from median size of under 4 (80% coverage) to 186 (55%), comparable to reported outbreaks in Canada and elsewhere. Outbreaks very often last under 60 days. We characterize how outbreak sizes and durations depend on the strength of interventions, community size and vaccination coverage. We make the model available as a web-based ‘shiny’ application.

Conclusions

Since the vast majority of measles cases in Canada can be traced to imported cases, our model serves as a last step in the chain of actions needed to bridge from global measles outbreaks to local scenarios within Canada. Given cases entering Canada, we are able to project the duration and size of an outbreak, helping to inform the public of the measles-related risk.
Medical deserts in Finland: measuring the accessibility and availability of primary health care services
Authors: Väisänen Visa , Satokangas Markku , Huhtakangas Moona , Antikainen Harri , Sinervo Timo
Published: February 2025

Background

Well-functioning primary health care (PHC) systems are needed to meet the challenges of aging populations and increasing care needs. However, “medical deserts”, areas with poor accessibility and availability of PHC services, remain a significant issue throughout Europe, contributing to regional inequalities. Identifying the location of these areas is crucial for effective policymaking and for improving health outcomes. Our aim was to locate underserved areas in Finland by developing a medical desert index. In addition, we examined the impact of telehealth, care needs, and multiple funding sources on the index and analyzed its association with key quality indicators.

Methods

The index was calculated using routinely collected municipality-level PHC consultation data from 2022 adjusted for population care needs (availability) and the average travel time to the nearest PHC center (accessibility). Telehealth and occupational healthcare consultations were included separately. Standardized index values were mapped and categorized using descriptive analysis, and compared with indicators of healthcare utilization, care accessibility and availability, care satisfaction, and continuity of care using correlation analysis.

Results

The index displayed clear patterns of medical deserts, primarily in the rural areas of northern and eastern Finland. Approximately 13% of the Finnish population resided in medical deserts, defined as a standard score of -0.5 or lower. The inclusion of telehealth consultations appeared to improve the index values especially in some rural areas. Better accessibility and availability of PHC services, as indicated through the index, was significantly correlated with lower proportion of acute care consultations, fewer hospital care days, and lower continuity of care among clients aged 65 years and older.

Conclusions

We were able to identify medical deserts in Finland utilizing novel methodology distinct from previous indicators, and thus providing important considerations for future research on regional inequalities in accessibility and availability of PHC services. Our findings demonstrated the potential of telehealth services in mitigating medical deserts, though its appropriateness for some population groups and care needs remains unclear. We call for health policy addressing PHC service provision especially in rural areas.
CircRNA hsa_circ_0004781 promoted cell proliferation by acting as a sponge for miR-9-5p and miR-338-3p and upregulating KLF5 and ADAM17 expression in pancreatic ductal adenocarcinoma
Authors: Lee Kun-Lin , Liu Jun-Jen , Huang Wei-Jan , Hung Ching-Sheng , Liang Yu-Chih
Published: February 2025

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of solid tumor, and novel strategies must be developed for treating it. Previous studies predominantly utilized circular RNA (circRNA) expression plasmids incorporating Alu elements to facilitate the indirect expression of circRNA.

Methods

Public databases and bioinformatics tools were used to identify hsa_circ_0004781 that is highly expressed in PDAC and its potential microRNA (miRNA) targets and corresponding mRNA targets. Real hsa_circ_0004781, which is identical to the native form of hsa_circ_0004781 without any exogenous sequences, was prepared through in vitro transcription by using a ribozyme and ion-pair reversed-phase high-performance liquid chromatography (IP-RP HPLC). The biological functions of hsa_circ_0004781 were evaluated using loss-of-function and gain-of-function approaches with circRNA expression plasmids and real hsa_circ_0004781.

Results

Knockdown of hsa_circ_0004781 inhibited the proliferation and migration of PDAC cells, whereas its overexpression produced opposite effects. Hsa_circ_0004781 was identified as a sponge for miR-9-5p and miR-338-3p, and its expression was negatively correlated with that of these miRNAs. Among the targets of miR-9-5p and miR-338-3p, Kruppel-like factor 5 (KLF5) and a disintegrin and metalloproteinase domain 17 (ADAM17) were negatively correlated with survival in patients with PDAC and were inversely regulated by these miRNAs. Furthermore, real hsa_circ_0004781 exhibited the same effects as those of the circRNA expression plasmids.

Conclusions

This study is the first to use real circRNAs to validate results obtained using circRNA expression plasmids. The results suggest that hsa_circ_0004781 functions as an oncogene, promoting the proliferation of PDAC cells through the miR-9-5p/KLF5 and miR-338-3p/ADAM17 axes. Therefore, hsa_circ_0004781 might be a therapeutic target for PDAC.
Alanine and glutathione targeting of dopamine- or ibuprofen-coupled polypeptide nanocarriers increases both crossing and protective effects on a blood–brain barrier model
Authors: Mészáros Mária , Phan Thi Ha My , Vigh Judit P. , Porkoláb Gergő , Kocsis Anna , Szecskó Anikó , Páli Emese K. , Cser Nárcisz M. , Polgár Tamás F. , Kecskeméti Gábor , Walter Fruzsina R. , Schwamborn Jens C. , Janáky Tamás , Jan Jeng-Shiung , Veszelka Szilvia , Deli Mária A.
Published: February 2025

Background

Targeting the blood–brain barrier (BBB) is a key step for effective brain delivery of nanocarriers. We have previously discovered that combinations of BBB nutrient transporter ligands alanine and glutathione (A-GSH), increase the permeability of vesicular and polypeptide nanocarriers containing model cargo across the BBB. Our aim was to investigate dopamine- and ibuprofen-coupled 3-armed poly(l-glutamic acid) nanocarriers targeted by A-GSH for transfer across a novel human co-culture model with induced BBB properties. In addition, the protective effect of ibuprofen containing nanoparticles on cytokine-induced barrier damage was also measured.

Method

Drug-coupled nanocarriers were synthetized and characterized by dynamic light scattering and transmission electron microscopy. Cellular effects, uptake, and permeability of the nanoparticles were investigated on a human stem cell-based co-culture BBB model with improved barrier properties induced by a small molecular cocktail. The model was characterized by immunocytochemistry and permeability for marker molecules. Nanocarrier uptake in human brain endothelial cells and midbrain organoids was quantified by spectrofluorometry and visualized by confocal microscopy. The mechanisms of cellular uptake were explored by addition of free targeting ligands, endocytic and metabolic inhibitors, co-localization of nanocarriers with intracellular organs, and surface charge modification of cells. The protective effect of ibuprofen-coupled nanocarriers was investigated against cytokine-induced barrier damage by impedance and permeability measurements.

Results

Targeted nanoformulations of both drugs showed elevated cellular uptake in a time-dependent, active manner via endocytic mechanisms. Addition of free ligands inhibited the cellular internalization of targeted nanocarriers suggesting the crucial role of ligands in the uptake process. A higher permeability across the BBB model was measured for targeted nanocarriers. After crossing the BBB, targeted dopamine nanocarriers subsequently entered midbrain-like organoids derived from healthy and Parkinson’s disease patient-specific stem cells. The ibuprofen-coupled targeted nanocarriers showed protective effects against cytokine-induced barrier damage.

Conclusion

BBB-targeted polypeptide nanoparticles coupled to therapeutic molecules were effectively taken up by brain organoids or showing a BBB protective effect indicating potential applications in nervous system pathologies.

Graphical Abstract
γ-Secretase modulator resistance of an aggressive Alzheimer-causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds
Authors: Trambauer Johannes , Sarmiento Rosa Maria Rodriguez , Garringer Holly J. , Salbaum Katja , Pedro Liliana D. , Crusius Dennis , Vidal Ruben , Ghetti Bernardino , Paquet Dominik , Baumann Karlheinz , Lindemann Lothar , Steiner Harald
Published: February 2025

Background

Amyloid-β peptide (Aβ) species of 42 or 43 amino acids in length (Aβ42/43) trigger Alzheimer´s disease (AD) and are produced in abnormal amounts by mutants of the γ-secretase subunit presenilin-1 (PS1), which represent the primary cause of familial AD (FAD). Lowering these peptides by γ-secretase modulators (GSMs) is increasingly considered a safe strategy to treat AD since these compounds do not affect the overall cleavage of γ-secretase substrates. GSMs were shown to modulate not only wild-type (WT) γ-secretase but also FAD mutants, expanding their potential use also to the familial form of the disease. Unlike most other FAD mutants, the very aggressive PS1 L166P mutant is largely resistant to GSMs. However, these data were mostly obtained from overexpression models, which mimic more the less relevant homozygous state rather than the heterozygous patient situation.

Methods

Mouse embryonic fibroblast and induced pluripotent stem cell-derived neuronal PS1 L166P knock-in (KI) cell models were treated with various GSMs and Aβ responses were assessed by immunoassays and/or gel-based analysis.

Results

We identified GSMs that lower Aβ42 and/or Aβ43 when PS1 L166P is heterozygous, as it is the case in affected patients, and could reduce the amount of pathogenic Aβ species towards WT levels. RO7019009 was the most potent of these compounds, reducing both pathogenic species and concomitantly increasing the short Aβ37 and Aβ38, of which the latter has been associated with delayed AD progression. Another effective compound, the structurally novel indole-type GSM RO5254601 specifically acts on the Aβ42 product line leading to a selective increase of the beneficial Aβ38. Interestingly, we further found that this class of GSMs can bind not only one, but both presenilin fragments suggesting that it targets γ-secretase at an unusual binding site.

Conclusion

Our data show that even highly refractory presenilin FAD mutants are in principle tractable with GSMs extending the possibilities for potential clinical studies in FAD with suitable GSM molecules.
Suitable scale structures for urban multi-functions: an integrative approach grounded in socio-ecological system analysis
Authors: Hong Wuyang , Yang Shuwen , Guo Renzhong , Li Yelin , Jiang Lin , Li Xiaoming
Published: February 2025

Aims

Research on the appropriate scale structure and spatial layout of ecological, urban, and agricultural spaces and the effective and methodical development and protection of urban space can provide a solid foundation for the sustainable development of the complex socio-economic urban environment.

Methods

Based on the perspective of a coupled social-ecological system, this paper constructed an assessment model to determine the ecological protection importance and development suitability of urban space, proposed the ecological-urban-agricultural priority for densely populated urban areas, and established the appropriate functional layout of urban space using a priority matrix-based mapping method.

Results

Through an empirical case study of Shenzhen, this paper determined the optimal scale structure of the types of functional spaces, identified areas of functional conflict, and proposed targeted optimization strategies for functional mismatch areas. The findings show that the appropriate scale ratio of Shenzhen’s urban, ecological, and agricultural functions is 5:4:1, which is consistent with the actual structure ratio of Shenzhen’s land use trends.

Conclusions

The proposed method can predict the appropriate scale structure of urban space development and ecological protection based on the comprehensive multi-perspective consideration of social and economic factors to provide a scientific reference for effective decision-making on urban space optimization and sustainable development.
“We need all hands on deck”: characterizing addiction medicine training in Canada—a mixed methods study of fellowship program directors
Authors: Lu Clara , Chan Kathryn , Martin Leslie , Fairbairn Nadia
Published: February 2025

Background

Addiction Medicine training in Canada has evolved substantially in the last few years with the establishment of accreditation standards and several new fellowship programs. The novelty of these formal training programs, created in response to complex and ever-expanding clinical needs in Addiction Medicine, creates unique educational circumstances that must be understood to support future growth. This study characterizes the current state of these postgraduate training programs in Canada through the perspectives of Program Directors (PDs).

Methods

This study is a mixed methods study of 12 PDs. In Phase 1, participants completed a quantitative survey analyzed through descriptive statistics. In Phase 2, participants underwent a qualitative semi-structured interview that was coded with a thematic analysis approach. Mixing occurred both during the interim analysis between phases and during the interpretation stage.

Results

28 trainees enrolled in a fellowship program in 2021–22 across 10 programs, and 27 trainees enrolled in 2022–23 across 11 programs. In each year, there were significantly fewer available spots than applications (31% and 29%, respectively). PDs identified a funding “bottleneck” as the most difficult and important challenge facing programs, with trainees supported by diverse and unstable funding sources. Qualitative analysis highlighted the need for sustainable funding models, flexibility toward alternative training pathways (shorter durations of training and re-entry from practice), and establishment of a national community of practice to support the co-creation of a robust addictions medical education infrastructure.

Conclusion

For Addiction Medicine training to meet workforce demands, PDs stressed that funding was the challenge of prime importance. Future studies should examine the perspectives of Addiction Medicine fellows, the clinical and research impacts of fellowship graduates, and the cost-effectiveness of fellowship funding models.
Recent updates on cold adaptation in population and laboratory studies, including cross-adaptation with nonthermal factors
Authors: Wakabayashi Hitoshi , Sakaue Hiroyuki , Nishimura Takayuki
Published: February 2025

This review aims to update our understanding of human cold adaptation. First, an overview of the thermoregulatory response to cold is provided, with some recent updates in human brown adipose tissue (BAT). Variation in BAT activity and multiorgan contributions to cold-induced thermogenesis were introduced. We found that individuals with less BAT activity rely more on shivering to compensate for less non-shivering thermogenesis (NST). The mechanisms of cold-induced vasoconstriction are summarized, including the role of arteriovenous anastomoses, adrenergic neural function, and inhibition of the nitric oxide vasodilator pathway. In addition, cold-induced vasodilation (CIVD) during cold immersion of the distal extremities is summarized with some recent updates in physiological mechanism. Furthermore, the cold shock response at the onset of cold immersion is introduced. Next, categorization of cold acclimatization/acclimation into habituation of shivering and metabolic and insulative adaptation are provided, with some recent updates. Especially, the rediscovery of human BAT has clarified metabolic acclimation, where increased NST replace shivering. Then, a greater CIVD response in populations in cold regions has been reported, whereas recent laboratory studies suggest no increase in CIVD after repeated cold exposure. To prevent cold injuries, individuals should not rely on habituation through repeated cold exposure. In addition, habituation to the cold shock response after repeated cold water immersion could help reduce the number of drownings. Furthermore, cross-adaptation between cold and nonthermal factors in the thermoregulatory response is summarized. Recent studies explored the relationship between exercise training and BAT activity, although this remains unresolved, depending on the exercise intensity and environmental conditions. The effects of exercise with cold exposure on the thermoregulatory response to cold are summarized in studies including divers working in cold water. We investigated the effect of exercise training in cold water, which resulted in increased muscle deoxygenation during submaximal exercise and greater anerobic power. Moreover, the effects of a hypoxic environment on cold adaptation are summarized. Elevated basal metabolism and higher distal skin temperature in highlanders could improve their cold tolerance. Finally, factors affecting cold adaptation are discussed. The type of cold adaptation may depend on the specific thermoregulatory responses repeated during the adaptation process.
Deep learning can reduce acquisition time of T2-weighted image in brain imaging
Authors: Abou-ELMagd Eman Hassan El-Saeed , Elmogy Sabry Alameldin , Abdelzaher Dina Gamal
Published: February 2025

Background

We used the deep learning-based reconstruction algorithm to reduce the scan time for brain T2-weighted images (T2WI) with reduction of image noise and preservation of image quality. The current prospective study included 22 cases; they were subjected to brain magnetic resonance. The aim was to investigate how much could deep learning reduce acquisition time of T2WI in brain imaging.

Results

There was a statistically significantly higher air noise (N) in conventional image analysis versus DL image analysis, but no statistically significant difference in image signal (S). Signal-to-noise ratio (SNR) was statistically significantly higher in DL image analysis versus conventional image analysis. This showed that the improvement in SNR was explained by significant decrease in N without significant change in S.

Conclusions

We concluded that deep learning-based reconstruction provides advantages of maintaining optimum image quality, reduction of image noise and obtaining the images in short time while applied during acquisition of brain magnetic resonance imaging (MRI) by T2WI. Yet, the diagnostic value of this technique to be verified, large-scale clinical studies should be conducted on this issue.
Clinical and epidemiological overview of hyperacute ischemic stroke patients treated with intravenous thrombolysis
Authors: Amalia Lisda , Qonitah Putri
Published: February 2025

Background

Hyperacute ischemic stroke is a type of ischemic stroke that occurs rapidly and suddenly due to blockage of blood flow to the brain, with onset within 0–24 h. The recommended treatment for hyperacute ischemic stroke patients is a recombinant tissue plasminogen activator (rtPA) according to the guidelines of the American Heart Association/American Stroke Association (AHA/ASA) and the European Stroke Organization (ESO). In Indonesia, there is still limited adoption of intravenous thrombolysis, and the researchers hope that hospitals in Indonesia will adopt this treatment for managing hyperacute ischemic stroke patients.

Objective

This study aims to describe the clinical characteristics of hyperacute ischemic stroke patients treated with intravenous thrombolysis.

Methods

This descriptive cross-sectional study was conducted at Dr. Hasan Sadikin Hospital in Bandung, which serves as the referral hospital for West Java for stroke cases treated with intravenous thrombolysis. The study employed total sampling from January 2021 to March 2024.

Results

From 23 patients, we found that most hyperacute ischemic stroke patients treated with intravenous thrombolysis were in the late elderly age group, 56–65 years old (43.5%), with onset within ≤ 4.5 h. Of the total sample, 91.3% of patients did not experience complications and approximately 50% of patients have good clinical and functional outcomes (based on NIHSS score).

Conclusion

This demonstrates the effectiveness of intravenous thrombolysis in managing hyperacute ischemic stroke patients. Future research should continue to explore optimal patient selection criteria and refine treatment protocols to further improve outcomes in stroke management.
3D fast forward modeling of DC resistivity data based on multiscale finite element method with oscillatory boundary conditions
Authors: Qi Yanfu , Zhao Yuhui , Cao Huake , Shu Chenchen , Zhou Jianmei
Published: February 2025

To achieve fast 3D forward modeling of the direct current resistivity method for large complex models, we develop a smooth multiscale finite element algorithm with oscillatory boundary conditions. The oscillatory boundary conditions of the multiscale basis functions are obtained by solving the boundary value problems of 2D partial differential equation on the surface of the multiscale elements, which can accurately describe the conductivity heterogeneity on the boundary of multiscale elements. Then, we construct the multiscale basis functions containing fine conductive structure information by solving the boundary value problems of the local 3D partial differential equation in the multiscale elements. With the help of the oversampling technique, we further reduce the resonance errors and improve the accuracy of the multiscale finite element method. Finally, the original current conduction problem is solved on a large-scale coarse mesh and the computational efficiency is improved. We verify the accuracy of the proposed algorithm by performing 3D multiscale forward modeling on a complex 3D ore-body model and comparing it with the traditional finite element method on fine mesh. On this basis, we further compare the numerical accuracy and calculation efficiency of linear- and oscillatory boundary conditions, and discuss the influence of conductivity contrast on the accuracy of the multiscale finite element method.
NAFLD vs MASLD (metabolic dysfunction associated steatotic liver disease) - why the need for a change of nomenclature?
Authors: Gastaldelli Amalia , Newsome Philip N
Published: February 2025

Several reasons led to the change in the nomenclature from non alcoholic fatty liver disease (NAFLD) to metabolic dysfunction associated steatotic liver disease (MASLD); the most important being limitations due to the reliance on exclusionary confounder terms and the use of potentially stigmatising language (the terms “nonalcoholic” and “fatty”). The new name was decided through a Delphi process and now includes in the name, and definition, the metabolic origin (the presence of at least 1 of 5 cardiometabolic risk factors) without the stigmatising terms. The recognition of a new category termed “metabolic and alcohol related/associated liver disease” (Met-ALD) opens up a new area for exploration although the relative contribution of alcohol and metabolic risk factors requires further evaluation as does the evidencing at a patient rather than population level.
Immune Dysregulation and Endometrial Receptivity Impairment in Women With Repeated Implantation Failure and Dyslipidemia
Authors: Zhang Yuan , Sun Xiaoya , Zhang YuanYuan , Zou Yangyun , Zhang Yue , Wang Jie , Gao Li , Ding Wei , Diao Feiyang , Liu Jiayin , Kwak-Kim Joanne Young Hee , Ma Xiang
Published: February 2025

Context

Dyslipidemia adversely affects reproduction outcomes; however, its relation with repeated implantation failure (RIF) remains unclear.

Objective

This study aims to analyze the impact of dyslipidemia on assisted reproductive technology (ART) outcomes, endometrial transcriptome, and microbiome of RIF women.

Design

A retrospective real-world analysis and prospective study.

Setting

University clinic.

Patients

6499 infertile women, including 5618 non-RIF and 881 RIF.

Interventions

Dyslipidemia.

Main Outcome Measures

Implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR) were compared in RIF women with or without dyslipidemia. Results of endometrial studies, including RNA sequencing (RNA-seq)-based endometrial receptivity test (ERT), 16S rRNA-based microbiome study, next-generation sequencing (NGS)-based gene comparison, and bulk RNA-seq deconvolution analysis were analyzed.

Results

The prevalence of dyslipidemia in RIF women was significantly higher. In dyslipidemia women, IR, CPR, and LBR were significantly lower, and the prevalence of nonreceptive ERT and the presence of endometrial pathogenic bacteria were higher than those of controls. After the personalized treatment, CPR 73.3% and LBR 60.0% were achieved in dyslipidemia women. NGS revealed that 176 differentially expressed genes in the endometrium of RIF women with dyslipidemia compared to those without, suggesting highly enriched in cholesterol and steroid biosynthesis and monocyte differentiation processes. An increased endometrial CD56dim natural killer cells and macrophage M1/M2 ratio with dysregulated immune factors were found by bulk RNA-seq deconvolution analysis.

Conclusion

RIF women with dyslipidemia have significantly poorer ART outcomes. In women with dyslipidemia, immune homeostasis was breached in the luteal phase endometrium, implicating a possible immune mechanism for dyslipidemia-related implantation failure.
Machine Learning-Based Biomarker Identification for Early Diagnosis of Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Boullion Jolie , Husein Amanda , Agrawal Akshat , Xing Diensn , Hossain Md Ismail , Bhuiyan Md Shenuarin , Rom Oren , Conrad Steven A , Vanchiere John A , Orr A Wayne , Kevil Christopher G , Bhuiyan Mohammad Alfrad Nobel
Published: February 2025

Aim

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an umbrella term for simple hepatic steatosis and the more severe metabolic dysfunction-associated steatohepatitis. The current reliance on liver biopsy for diagnosis and a lack of validated biomarkers are major factors contributing to the overall burden of MASLD. This study investigates the association between biomarkers and hepatic steatosis and stiffness measurements, measured by FibroScan®.

Methods

Data from the National Health and Nutritional Examination Survey (2017-2020) was collected for 15,560 patients. Propensity score matching balanced the data with a 1:1 case-to-control for age and sex allowing for preliminary trend assessment. Random Forest machine learning determined variable importance for the incorporation of key biomarkers (age, sex, race, BMI, HbA1C, PFG, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, ALT, AST, ALP, albumin, GGT, LDH, iron, total bilirubin, total protein, uric acid, BUN, and hs-CRP) into logistic regression models predicting steatosis (MASLD indicated by a controlled attenuation parameter™ score of >238 dB/m) and stiffness (hepatic fibrosis indicated by a median liver stiffness >7 kPa). Sensitivity analysis using XGBoost and Recursive Feature Elimination was performed.

Results

The Random Forest models (the most accurate) predicted MASLD with 79.59% accuracy (p<0.001) and specificity of 84.65% and, hepatic fibrosis with 86.07% accuracy (p<0.001) and sensitivity of 98.01%. Both the steatosis and stiffness models identified statistically significant biomarkers, with age, BMI, and insulin appearing significant to both.

Conclusion

These findings indicate that assessing a variety of biomarkers, across demographic, metabolic, lipid, and standard biochemistry categories, may provide valuable initial insights for diagnosing patients for MASLD and hepatic fibrosis.
The genome sequence of the Small Red Damselfly, Ceriagrion tenellum (de Villers, 1789)
Authors: Sivell Olga , Sivell Duncan , Mitchell Ryan , Webb Judy ,   Natural History Museum 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: February 2025

We present a genome assembly from a male specimen of Ceriagrion tenellum (Small Red Damselfly; Arthropoda; Insecta; Odonata; Coenagrionidae). The genome sequence has a total length of 2,077.00 megabases. Most of the assembly (99.28%) is scaffolded into 14 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.21 kilobases in length.
The genome sequence of the Marsh Click-beetle, Actenicerus siaelandicus (Müller, O.F., 1764)
Authors: Sivell Olga , Mitchell Ryan , Geiser Michael  F. ,   Natural History Museum 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: February 2025

We present a genome assembly from a female specimen of Actenicerus siaelandicus (Marsh Click Beetle; Arthropoda; Insecta; Coleoptera; Elateridae). The genome sequence has a total length of 854.91 megabases. Most of the assembly (95.23%) is scaffolded into 10 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.17 kilobases in length.
The genome sequence of the Antarctic lanternfish, Electrona antarctica (Günther, 1878)
Authors: Bista Iliana , Collins Martin ,   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
Published: February 2025

We present a genome assembly from an individual female Electrona antarctica (the Antarctic lanternfish; Chordata; Actinopterigii; Myctophiformes; Myctophidae). The genome sequence has a total length of 1,427.40 megabases. Most of the assembly is scaffolded into 24 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 20.02 kilobases in length.
Management by Originals: Inventor CEOs and Firms’ Strategic Change
Authors: Kang Yungu , Zhu David
Published: February 2025

We build upon theories and studies regarding inventors and strategic leadership to explain how inventor CEOs are likely to drive a firm’s strategic change. We explain why inventor CEOs have the unique attributes of divergent thinking and intrinsic motivation and, accordingly, pursue strategies that deviate from the past. We further suggest that the positive relationship between inventor CEO status and strategic change is strengthened by CEO liberalism, CEO career variety, and industry dynamism. Using a comprehensive longitudinal database of S&P 1500 firms, we test our theoretical predictions and find empirical support for most of our hypotheses except for the moderating effect of industry dynamism. In highlighting the prevalence of inventor CEOs and showing how this achievement-based experience of CEOs is related to strategic change, our study identifies an important and novel antecedent of this important strategic outcome.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/stsc.2023.0058 .
The non-symmetric strong multiplicity property for sign patterns
Authors: Curtis Bryan , Garnett Colin , Shader Bryan L. , Vander Meulen Kevin N.
Published: February 2025

We develop a non-symmetric strong multiplicity property for matrices that may or may not be symmetric. We say a sign pattern allows the non-symmetric strong multiplicity property if there is a matrix with the non-symmetric strong multiplicity property that has the given sign pattern. We show that this property of a matrix pattern preserves multiplicities of eigenvalues for superpatterns of the pattern. We also provide a bifurcation lemma, showing that a matrix pattern with the property also allows refinements of the multiplicity list of eigenvalues. We conclude by demonstrating how this property can help with the inverse eigenvalue problem of determining the number of distinct eigenvalues allowed by a sign pattern.