bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of abaloparatide on fracture incidence and bone mineral density in postmenopausal women with osteoporosis at highest risk for fracture
Authors: DeSapri Kristi Tough , Clarke Bart L. , Kostenuik Paul , Wang Yamei , Mitlak Bruce H.
Published: February 2025

Objective

This post hoc analysis evaluated the efficacy of abaloparatide treatment in a subgroup of postmenopausal women from the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE; NCT01343004) study who met high fracture risk criteria (defined in several professional society guidelines).

Methods

Women from ACTIVE meeting ≥1 of the following fracture risk criteria were included: fracture within the past 12 months or prevalent vertebral fracture, baseline T score of <−3.0 at any site, very high fracture risk probability by FRAX (ie, 10-yr major osteoporotic fracture >30% or hip fracture >4.5%), or multiple prior fractures at baseline since age ≥45 years.

Results

A total of 2,026 participants met ≥1 fracture risk criteria defined in clinical guidelines (abaloparatide, n = 664; placebo, n = 677; teriparatide, n = 685). New vertebral fracture risk was reduced in participants receiving abaloparatide (4 [0.72%]) and teriparatide (6 [0.99%]) versus placebo (28 [4.77%]; both P < 0.0001). Estimated Kaplan-Meier cumulative incidence of nonvertebral fracture was 3.0%, 5.3%, and 3.0% in the abaloparatide, placebo, and teriparatide groups, respectively; 4.0%, 9.0%, 4.3% for clinical fracture; 1.6%, 6.8%, 3.0% for major osteoporotic fractures; and 1.1%, 2.1%, 2.1% for wrist fracture. Abaloparatide was associated with bone mineral density gains from baseline at the lumbar spine, total hip, and femoral neck at all time points (6, 12, and 18 mo; P < 0.0001 for all). Common adverse events reported in participants treated with abaloparatide were hypercalciuria (11.5%), dizziness (11.0%), and arthralgia (8.9%).

Conclusions

Abaloparatide reduced fracture incidence and increased bone mineral density in participants at highest fracture risk, consistent with the overall ACTIVE study.
Climate change and cardiovascular risk
Authors: Ang Song Peng , Chia Jia Ee
Published: February 2025

Purpose of review

This review explores the complex relationship between climate change and cardiovascular health. It examines the mechanisms through which climate change impacts cardiovascular risk, highlights recent findings on regional trends, and discusses mitigation strategies.

Recent findings

Climate change significantly contributes to cardiovascular morbidity and mortality through mechanisms such as temperature extremes, air pollution, and food insecurity. Heatwaves increase risks of dehydration, electrolyte imbalance, and acute cardiovascular events, while cold spells exacerbate myocardial stress and pollution-related cardiovascular risks. Air pollution, including fine particulate matter (PM2.5), induces systemic inflammation, endothelial dysfunction, and atherosclerosis. Emerging data highlight regional variations, with urbanization exacerbating risks in Asia-Pacific and Middle Eastern populations, while extreme heat and cold challenge resilience in Europe and Latin America. Studies also link socioeconomic stress from climate-induced displacement and resource shortages to chronic cardiovascular conditions. Notably, urban greening and air quality regulations demonstrate potential for reducing cardiovascular risks.

Climate change amplifies cardiovascular risks through diverse mechanisms, disproportionately affecting vulnerable populations. Targeted strategies, including public health campaigns, sustainable urban planning, and technological innovations, can mitigate these risks. Advances in generative artificial intelligence and big data analytics offer opportunities to tailor interventions and enhance predictive modeling. A multidisciplinary approach integrating public health, environmental science, and clinical expertise is critical to addressing these challenges. Urgent action is required to mitigate the long-term cardiovascular impacts of climate change and foster resilient health systems globally.
Advances in device-based therapies for cardiorenal syndrome
Authors: Esposito Michele L. , Moore Ryan
Published: February 2025

Purpose of review

Diuretic resistance presents a harrowing obstacle in patients with decompensated heart failure and cardiac-driven cardiorenal syndrome. This conundrum not only presents clinical decision-making challenges but also portends worse outcomes for these patients. The development of device-based therapies to provide support in these cases is an attractive alternative therapeutic option. This review will describe the growing evidence supporting developments in device-based therapies for cardiorenal syndrome in patients with heart failure.

Recent findings

We describe multiple emerging technologies in this space, each classified according to its mechanism of action. ‘Pushers’ are devices that increase blood flow and perfusion pressure to the renal arteries. ‘Pullers’ reduce renal afterload by decreasing pressure in the renal veins, and ‘fluid shifters’ decongest the interstitium through the lymphatic system.

While early results from small clinical studies piloting these devices are promising, randomized controlled trials are needed to fully evaluate their utility in patients with heart failure. In the future, these devices may work synergistically with pharmacologic therapy to reduce average inpatient length of stay, hospitalization rates, and potentially improve mortality.
Evaluating the association of clinical cardiovascular parameters and metabolic indices with levels of cystatin C in early middle age
Authors: Ashour Laith , Jarrar Zeid , Alzoubi Ghada , Hamdan Samar , Heramas Rima , Alakhdar Dima , Abu Jeries Julie , Mishleb Areen , Marar Maher , Ayesh Layan , Abu Sirhan Lina A.
Published: February 2025

Background:

The pathophysiology of renal dysfunction requires population-based study. It is debatable in the literature whether cardiovascular metrics have an impact on cystatin C levels.

Methods:

using public-use biomarkers data of The National Longitudinal Study of Adolescent to Adult Health (Add Health) Wave 5 data, we tested, after adjusting for age (range: 32–42), anthropometrics (Body Mass Index (BMI), waist circumference, and arm circumference), HbA1C, Low-Density Lipoprotein (LDL), triglyceride, smoking, and sex, the association of five clinical cardiovascular measures (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, and pulse rate) with cystatin C levels. Multiple linear regression analysis with a design-based approach was employed for data analysis after log-transformation of cystatin C levels.

Results:

Our findings showed that there was no significant association between cystatin C levels and any of the previously mentioned cardiovascular parameters in this age group (P > 0.05). However, there was a significant association between cystatin C levels and age (Exponentiated estimate (EE) (percent increase per unit) =1.21; 95% CI=[0.97, 1.103], P < 0.0001), BMI and waist circumference (EE= 0.702; 95% CI=[0.7, 0.705], P < 0.0001), triglycerides level (EE=0.02; 95% CI=[0.0199, 0.0201], P = 0.01), smoking status (EE (compared to nonsmokers)=8.98, 95% CI=[8.95, 9.01], P < 0.0001), and female sex (EE (compared to males)= -5.92; 95% CI=[-5.94, -5.89], P < 0.0001).

Conclusions:

Our findings clarify the impact of confounding factors, particularly age, on cystatin C levels. They also demonstrate how the significant correlation between cardiovascular parameters and cystatin C levels that seen in earlier studies is largely affected by the age. Anthropometrics, age, lipid indices, and smoking should all be considered in clinical practice as possible reasons for increased cystatin C levels in otherwise healthy middle-aged individuals.
Research Letter: Rehabilitation Planning Using Rasch Analysis of the Mayo-Portland Adaptability Inventory, 4th Edition
Authors: Malec James F.
Published: February 2025

Objective: To present a method for examining associations among items and total T-score for the Mayo-Portland Adaptability Inventory (4th edition; MPAI-4) that can assist in rehabilitation planning. Setting: Advanced postacute brain injury rehabilitation programs. Method: Description and presentation of a rehabilitation planning guide based on Rasch analysis of the MPAI-4 and application in 2 cases of participants with traumatic brain injury. Results: Initial individualized rehabilitation treatment recommendations derived from examination of the rehabilitation planning guide for specific participants are described. Conclusions: Systematic examination of a visual depiction of associations among MPAI-4 items and total T-score identified through Rasch analysis is useful for rehabilitation planning and in communication and education with participants and families.
Transcriptional Profiling of Patients With Fuchs Endothelial Corneal Dystrophy With and Without Trinucleotide Repeat Expansion in TCF4
Authors: Nakagawa Tatsuya , Tokuda Yuichi , Nakano Masakazu , Tateishi Ayana , Yasunaga Mari , Tourtas Theofilos , Schlötzer-Schrehardt Ursula , Kruse Friedrich , Tashiro Kei , Koizumi Noriko , Okumura Naoki
Published: February 2025

Purpose:

To investigate transcriptomic differences between patients with Fuchs endothelial corneal dystrophy (FECD) with and without trinucleotide repeat (TNR) expansion in the transcription factor 4 gene, as the genetic basis for patients with FECD lacking TNR expansion remains unclear.

Methods:

Bulk RNA sequencing was performed on corneal endothelial cells from 17 subjects: 10 patients with FECD [4 with repeat expansion lengths <50 (RE−) and 6 with expansions of 50 or more (RE+)] and 7 controls. Differential gene expression analysis was conducted using DESeq2. Principal component analysis (PCA), correlation matrix analysis, and heatmap visualization were used to evaluate gene expression patterns. Gene Ontology enrichment analysis was performed on differentially expressed genes (DEGs).

Results:

Analysis identified 509 DEGs (281 upregulated, 228 downregulated) between RE− and controls, and 640 DEGs (292 upregulated, 348 downregulated) between RE+ and controls. PCA revealed distinct gene expression patterns in both RE− and RE+ groups compared with controls. Between RE− and RE+ groups, only 10 DEGs were identified: ALDH3A1, ENSG00000286252, RNU6-645P, SNORD113-7, RNU6-429P, SNORA16A, COCH, EGFL6, SEMA3E, and ENSG00000228463. PCA, correlation matrix analysis, and heatmap visualization demonstrated high similarity in overall gene expression patterns between RE− and RE+ groups.

Conclusions:

Contrary to expectations, gene expression profiles showed remarkable similarity between patients with FECD with and without TNR expansion. Further investigation of the identified DEGs may provide insights into the role of TNR expansion in FECD pathophysiology.
Laparoscopic simulation training improves operating room performance of surgical residents: a multicenter randomized trial (NOVICE)
Authors: Thomaschewski Michael , Vonthein Reinhard , Keck Tobias , Laubert Tilman , Benecke Claudia
Published: February 2025

Background:

Learning basic laparoscopic skills can be efficiently performed ex vivo in a safe environment using simulation devices. However, in many countries, the broad and mandatory implementation of ex vivo laparoscopic simulation training in surgical residency is still lacking. The aim of the study was to evaluate the efficacy of laparoscopic basic skills simulation training on the surgical performance of residents during their first laparoscopic procedures in the operating room.

Methods:

This was a multicenter, prospective, randomized, two-arm, single-blind trial. The study recruited first-year surgical residents (NOVICE) with no previous personal experience in laparoscopic surgery. After the participants had performed their first laparoscopic cholecystectomy, they were randomized into two groups: the intervention group underwent six weeks of standardized laparoscopic basic skills simulation training (Lübeck Toolbox Curriculum), whereas the control group did not. After six weeks, both groups performed a second cholecystectomy. The videotapes of the first and second cholecystectomies were evaluated blinded based on the Global Operative Assessment of Laparoscopic Skill (GOALS) score. The primary endpoint was the changes in the GOALS scores between the first and second cholecystectomies.

Results:

22 surgical residents from 11 surgical clinics in Germany were included, and 4 residents dropped out. The median improvement in the LTB-Curriculum group between CHE I and CHE II was 8.5 GOALS score points in contrast to 2 points in the control group. This difference was statistically significant (95%CI: 1–15 points, P = 0.013).

Conclusion:

Ex-vivo training in basic laparoscopic skills significantly improved the surgical performance of residents during their first laparoscopic cholecystectomies in the operating room.
Augmented reality guided versus computed tomography guided percutaneous lung nodule localization: a noninferiority randomized clinical trial
Authors: Song Zuodong , Li Yin , Tian Qing , Sun Chao , Liu Hongfeng , Chong Kongyong , Zhang Qian , Chen Jianeng , Li Pengchong , Song Liwei , Tosi Davide , Kim Min P. , Zhebing Lin , Luo Qingquan , Yu Lingming , Cheng Xinghua
Published: February 2025

Hypothesis:

This study hypothesized that augmented reality (AR) technology has comparable accuracy and safety to conventional CT localization in guiding percutaneous transthoracic lung puncture (PTLP) to localize small pulmonary nodules.

Methods:

This study was a prospective, non-inferiority randomized clinical trial. Patients were randomly assigned between 23 May 2023, and 26 September 2023. Patients with small peripheral lung nodules (≤2 cm) were recruited.

Patients were randomly assigned to either the CT-guided PTLP group or the AR-guided PTLP group, with a 1:1 allocation ratio. The primary outcome was the accuracy of lung nodule localization measured by localization error. The secondary outcomes included procedure duration, radiation exposure dosage and complications.

Results:

A total of 70 patients underwent either CT- or AR-guided lung nodule localization and subsequent surgeries. Localization error was smaller in the AR-guided group than in the CT-guided group (mean ± SD, 3.1 ± 4.0 mm vs. 5.4 ± 4.2 mm, P = 0.026). The mean difference of localization errors was −2.3 mm (95% CI: − 4.2 to −0.3 mm, P < 0.001 for non-inferiority). Compared to the CT-guided group, the AR-guided group demonstrated significantly lower radiation exposure (mean ± SD, 421 ± 168 vs. 694 ± 229 mGy × cm, P < 0.001) and shorter localization procedure duration (mean ± SD, 8.8 ± 2.3 vs. 14.1 ± 1.8 minutes, P < 0.001), with no statistical difference in complications.

Conclusions:

The accuracy of the AR-guided approach is comparable to that of the CT-guided approach in localizing small lung nodules. Furthermore, the utilization of AR technology has been demonstrated to reduce procedural time and minimize radiation exposure for patients.
Real-world Effectiveness of Dupilumab in Eosinophilic Esophagitis
Authors: Garg Archit , Moond Vishali , Velpari Sugirdhana , Broder Arkady , Mohan Babu P.
Published: February 2025

Background:

Dupilumab is the only FDA-approved medication for eosinophilic esophagitis (EoE). Clinical trials have shown its effectiveness in alleviating symptoms and decreasing inflammation associated with EoE. However, real-world data on its efficacy is still limited.

Methods:

We searched multiple databases for articles reporting the outcomes of dupilumab for the treatment of EoE and conducted a meta-analysis.

Results:

Five retrospective studies including 209 subjects (mean age: 22.12±12.01 y and 61.24% males) were analyzed. The pooled outcome for symptom improvement with dupilumab was 89.2% [95% Cl: 68.0%-97.0%; I
2=58%]. Peak eosinophil count improved markedly postdupilumab [pre: 47.13 (95% Cl: 45.5-48.67; I
2=98%) vs. post: 6.44 (95% Cl: 0.72-13.60; I
2=98%) eos/hpf, P<0.001]. There was a significant reduction in Endoscopic Reference Score (EREFS) [pre: 4.10 (95% Cl: 1.74-6.43; I
2=95%) vs. post: 0.77 (95% Cl: 0.14-1.7; I
2=95%), P<0.001]. The mean duration of treatment and follow-up was 5.66±1.14 months. The most common adverse event reported was a pain due to injection, which was controlled with local anesthetics.

Conclusion:

Our study shows that in a real-world scenario, administration of dupilumab for EoE induces histologic and endoscopic remission and symptomatic improvement. Hence, dupilumab can be considered a treatment option for EoE, especially in resistant cases. Future studies should evaluate its long-term effectiveness for preventing esophageal fibrosis/stricture and long-term side effect profile. Furthermore, cost-effectiveness analysis is warranted to help establish its role as a potential first-line treatment strategy.
Psychedelic-assisted Therapy as a Promising Treatment for Irritable Bowel Syndrome
Authors: Mauney Erin , King Franklin , Burton-Murray Helen , Kuo Braden
Published: February 2025

Irritable bowel syndrome (IBS) is prevalent and can be disabling. Many patients remain symptomatic despite behavioral and medical therapies. Psychedelic-assisted therapy (PAT), in which serotonergic agents like psilocybin are administered in a psychotherapeutic context, has shown promise for refractory psychiatric disorders, including major depressive disorder and post-traumatic stress disorder. Emerging evidence suggests PAT may also be beneficial for chronic pain conditions, including fibromyalgia, low back pain, and migraines. IBS is highly comorbid with depression, anxiety, and other chronic pain disorders, suggesting shared cognitive and neurological roots and potentially shared therapeutic targets. In this editorial, we discuss 3 lines of evidence for PAT as a treatment for IBS, under the overarching themes of (1) psychological mechanisms (the findings from historic studies of psychedelics for chronic pain and the elements of psychobiological dysfunction targeted by PAT), (2) central nervous system mechanisms (default mode network modulation and induction of neuroplasticity), and (3) the neurointestinal pathophysiology of IBS that may be modified by PAT. We argue that this evidence suggests PAT is worthy of study as a new therapy for IBS, and potentially for other disorders of gut-brain interaction (DGBI). Successful application of PAT to gastrointestinal disease would represent a major step beyond mind-body dualism, with potential implications for other functional somatic disorders.
Lean Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Desai Chaula , Lohani Sweta , Sharma Anuj R. , Schwartz Lucas , Gujjula Saigopal R. , Baskar Adhithya , Baskar Udhaya , Baskar Suriya , Vasikaran Anush
Published: February 2025

Goals:

To compare outcomes of MASLD in obese and nonobese populations.

Background:

MASLD is emerging as one of the leading causes of liver failure and liver-related morbidity and mortality, with an increasing prevalence in the nonobese or lean population. The purpose of this study is to compare hepatic and oncological outcomes between MASLD patients with lean BMI and nonlean BMI.

Study:

The National Inpatient Sample (NIS) was queried from 2016 to 2020 for adult hospitalizations with MASLD. Exclusion criteria included concurrent diagnoses of viral hepatitis, alcoholic hepatitis, primary biliary cholangitis, hereditary hemochromatosis, autoimmune hepatitis, or Wilson disease. Outcomes of MASLD and its complications were compared between the lean and nonlean subgroups.

Results:

Patients with lean BMI had higher mortality rates (odds ratio: 2.10, P<0.001). The lean cohort also had higher odds of cirrhosis, portal hypertension, SBP, and ascites. The lean subgroup had higher odds of gastrointestinal malignancies including esophageal cancer, gastric cancer, pancreatic cancer, and colorectal cancer.

Conclusions:

Hospitalized lean MASLD patients had higher odds of mortality, ​​hepatic morbidities, and gastrointestinal malignancies. These results challenge the use of BMI as a predictor of morbidity and mortality for MASLD patients. Future studies should focus on therapeutic options for MASLD and compare their efficacies between lean and nonlean populations.
The Study of Anorectal Function Using High-resolution Anorectal Manometry in Patients With Fecal Impaction
Authors: Ciriza de los Ríos Constanza , Aparicio Cabezudo Marta , Zatarain Valles Ana , García Pravia Laura , Rey Díaz Rubio Enrique
Published: February 2025

Aim:

This study aims to evaluate anorectal function through high-resolution anorectal manometry (HRAM) in patients with constipation and fecal impaction, considering the limited information available on this subject.

Materials and Methods:

HRAM conducted between January 2021 and November 2023 (785 procedures) were reviewed. Patients were identified as individuals who experienced at least one episode of hard stools in the last year that were unable to evacuate. They were compared with constipated patients without fecal impaction episodes (control group). HRAM was performed using solid-state equipment (Medtronic). Logistic regression analysis was done to identify demographic-clinical factors and manometric variables associated with fecal impaction.

Results:

Fecal incontinence was independently associated with fecal impaction [adjusted odds ratio (aOR): 20.4, 95% CI: 2.5-167.8] after adjusting for demographic and clinical variables. Severe rectal hyposensitivity (no perception of urgency from a volume of 200 mL) was present in 38.2% of patients with fecal impaction and 5.9% of controls (P=0.001). Defecatory dyssynergia was diagnosed in 29.4% of patients with fecal impaction. Lower squeeze pressure and severe rectal hyposensitivity were independently associated with fecal impaction with an aOR of 0.98 (95% CI: 0.98-0.99) and aOR of 10.4 (2-54.1), respectively, and after adjusting for all manometric parameters. Hypotonia and hypo-contractility of the anal canal were found in 53.8% and 46.2% of patients with fecal impaction and incontinence, respectively.

Conclusion:

Patients with fecal impaction often show rectal hyposensitivity and anal hypo-contractility, which are independent risk factors for impaction. Fecal incontinence is linked to fecal impaction, and their coexistence is associated with reduced anal canal pressures.
The clinical challenge of managing patients after sustained virological response with direct-acting antivirals for Hepatitis C
Authors: Pocurull Anna , Lens Sabela
Published: February 2025

Purpose of review

This review highlights the critical considerations for monitoring patients who achieve sustained virological response (SVR) after direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection. Despite the remarkable success of DAAs, challenges persist in managing long-term risks, including hepatocellular carcinoma (HCC), liver decompensation, and extrahepatic manifestations, necessitating a tailored follow-up approach.

Recent findings

Recent studies emphasize that SVR does not eliminate risks for complications, particularly in patients with advanced fibrosis or cirrhosis. Advances in noninvasive tools, such as transient elastography and blood-based markers, have improved assessment of portal hypertension and liver function dynamics post-SVR. HCC surveillance remains critical for high-risk groups. Additionally, SVR improves extrahepatic conditions like mixed cryoglobulinemia and non-Hodgkin lymphoma, though careful monitoring for recurrence or associated risks is advised. Reinfection in high-risk populations underscores the importance of structured prevention and retreatment strategies.

Tailored follow-up of post-SVR patients remains essential. Future research should focus on refining predictive tools for late complications and optimizing surveillance strategies, balancing cost-effectiveness with clinical outcomes.
Panenteric capsule endoscopy in gastrointestinal bleeding – time to change old habits?
Authors: Segatta Francesco , Paggi Silvia , Radaelli Franco , Rondonotti Emanuele
Published: February 2025

Purpose of review

Capsule endoscopy (CE) is an effective tool for small bowel evaluation. Recent technical advancements, including long-lasting batteries and enhanced optics, have enabled featured capsules (panenteric capsules, PCs) to potentially assess the entire gastrointestinal (GI) tract. The PC provides a potential easy-to-use, comprehensive, single-device approach for evaluating GI bleeding patients. This review critically examines the potential role of PC in patients with GI bleeding by highlighting benefits, limitations, open issues, and future challenges.

Recent findings

Evidence on PC for GI bleeding patients remains limited. Two retrospective studies and one recent prospective trial consistently show that when used in the workup of GI bleeding patients, PC is safe, feasible, achieves high diagnostic yield (both in the small and large bowel), and potentially reduces the need for unnecessary colonoscopies. Nevertheless, current challenges include the need for extensive bowel preparation, incomplete colon evaluation, and limited access to trained readers.

The PC holds promise for optimizing the diagnostic workup of GI bleeding patients. However, significant challenges remain. Robust clinical trials comparing standard diagnostic methods to PC-based workup are needed before the adoption of PC in managing bleeding patients in clinical practice.
Portal hypertension in pregnancy
Authors: Pint Dorien , Chung Yooyun , Heneghan Michael A.
Published: February 2025

Purpose of review

This review highlights the management, maternal and fetal outcomes, and the critical role of prepregnancy counseling for women with portal hypertension (PHT), a topic of growing clinical relevance as pregnancies in women with PHT have increased over the last two decades.

Recent findings

Pregnancy exacerbates PHT due to physiological changes that increase blood flow and vascular resistance, raising the risk of life-threatening complications like variceal bleeding. The distinction between noncirrhotic (NCPH) and cirrhotic portal hypertension (CPH) is essential, as maternal risks vary significantly.

Optimal care for women with PHT requires preconception counseling to assess risks, adjust medications, and plan necessary investigations such as variceal and splenic artery aneurysm screening and, if necessary, plan additional interventions. A multidisciplinary team – including hepatologists, obstetricians, anesthetists, and radiologists – is crucial for personalized management, addressing both the mode of delivery and peripartum care. While PHT complicates pregnancy, favorable outcomes are achievable with proactive planning and close follow-up during pregnancy.
A metric-based image-formation model explains the improvement in subjective refraction using temporal defocus waves
Authors: Rodriguez-Lopez Victor , Dorronsoro Carlos , de Castro Alberto
Published: February 2025

SIGNIFICANCE

Direct subjective refraction (DSR) is a novel method for refractive error measurements that uses temporal changes in defocus and a flicker minimization task. The computational models developed here are a framework for improving this clinical method.

PURPOSE

This study aimed to model the measurement of refractive error with the DSR method, which uses rapid changes in optical power and a bichromatic (red/blue) stimulus.

METHODS

The polychromatic point spread function of the eye was used to simulate the retinal image projected in DSR method, and an image quality (IQ) metric was defined based on the spatial frequencies of the retinal image. Three tasks were modeled: blur minimization (BM), monochromatic flicker minimization (MFM), and polychromatic flicker minimization or DSR. A metric was defined for each task and studied through focus in a ±3-D range. Whereas BM was modeled using only the IQ of the projected images, MFM and DSR metrics were a function of the IQ of the average retinal image and a metric to quantify the similarity (flicker) in the image. The width of the through-focus peak was used to compare between tasks, and different values of pupil size and spherical aberration were studied.

RESULTS

The through-focus 90% peak width was 0.48, 0.16, and 0.19 D for BM, MFM, and DSR tasks, respectively, which agreed well with previous experimental data. The 90% peak width increased for small pupils and with increasing values of spherical aberration in BM and MFM, but it remained relatively constant in DSR model.

CONCLUSIONS

The developed models explained previous experimental findings that reported a higher repeatability of the DSR compared with the traditional refraction method.
Knowledge, Awareness, Practices, and Perceptions of Risk and Responsibility Related to Extreme Heat:
Authors: Tetzlaff Emily J. , Meade Robert D. , O’Connor Fergus K. , Kenny Glen P.
Published: February 2025

Objectives:

Knowledge and risk perception are driving factors for initiating appropriate health-protective actions during extreme heat events (EHEs). We sought to examine the (1) current knowledge of heat as a health threat, (2) perception of personal vulnerability to heat, (3) role of heat warnings and heat alert and response systems in initiating heat mitigating practices, and (4) opinions of community preparedness among heat-vulnerable older adults, as well as explore factors that may influence these concepts.

Design:

Cross-sectional survey.

Setting:

Canada.

Participants:

Individuals aged 50 years or older.

Main Outcome Measures:

The number of respondents and percentage of the total sample were calculated based on individual response rates to each question. To explore factors that may have influenced the respondents’ understanding of heat health knowledge, awareness, and risk perception, a bootstrapped least absolute shrinkage and selection operator regression was conducted.

Results:

1027 respondents (69% female, median age: 68 years) from 10 provinces/territories. Most felt knowledgeable about heat stress (74%), but many indicated that greater effort is needed to increase public awareness of EHE (64%). Self-reported responsiveness to heat alerts was also high (88%) despite many respondents reporting a low level of self-perceived risk (66%) and characteristics of heat susceptibility (eg, age, comorbidities).

Conclusions:

In our sample of older Canadians, various factors influenced knowledge, perceived heat vulnerability, responsiveness to heat alerts, and perception of community preparedness. These findings can help inform public heat preparedness initiatives to ensure they align with the needs of older Canadians.
Intense Prostate-specific Membrane Antigen Avid Hepatic Metastatic Lesions Shortly After Finishing 6 Cycle Pluvicto Treatment
Authors: Wang Xiaofei , Hogan Thomas , Heubach Kody
Published: February 2025

A 71-year-old man was diagnosed with prostate cancer in 2012. After treatment with hormone, chemo, and combinations subsequently, the baseline prostate-specific membrane antigen PET scan revealed 130+ nodal and osseous metastatic lesions. After 4 doses of pluvicto, a partial response was appreciated. However, new intense prostate-specific membrane antigen avid hepatic lesions occupied around 30% of the liver with poorly differentiated metastatic prostate cancer 55 days after the last dose of pluvicto and markedly elevated prostate-specific antigen. This case highlights the need for vigilant monitoring and alternative treatment strategies.
Comparative Efficacy of Regenerative Therapies for Diabetic Foot Ulcers
Authors: Yang Hsi-An , Hsu Ren-Jun , Jheng Wun-Long , Weng Feng-Ju , Lee Jian-Jr
Published: February 2025

Background

Diabetic foot ulcer (DFU) is one of the most dreaded complications of diabetes mellitus and is associated with a high risk of lower limb amputation and mortality. Because the efficacy of conventional treatments for DFUs is often limited, regenerative medicine therapy, such as growth factors and stem cells, may provide a solution to chronic wound healing. In this study, we compared several kinds of regenerative therapy for treating DFUs in terms of efficacy.

Methods

We systemically searched relevant studies on PubMed, Cochrane Library, and EMBASE. Randomized clinical trials on conventional treatment combined with platelet-rich plasma (PRP), epidermal growth factor (EGF), or stem cell therapy, compared with conventional treatment alone in patients with DFUs, were included in this study.

Results

A total of 1454 patients from 23 randomized controlled trials (RCTs) were included in the network meta-analysis. In terms of the number of completely healed ulcers, no significant difference was noted between PRP, stem cell therapy, and EGF group. We also performed surface under the cumulative ranking curve analyses to predict the rank of each intervention by the number of completely healed ulcers. The predicted ranking was as follows: stem cell, PRP, EGF, and the control group (conventional treatment alone). Furthermore, when we compared the mean of the wound healing time of DFUs among these four interventions, we found that the PRP group achieved significantly earlier ulcer healing than the stem cell, EGF, and control groups. No significant difference was observed in the time needed for wound healing between the stem cell and EGF groups. Funnel plot analysis demonstrated no publication bias.

Conclusions

PRP combined with conventional treatment significantly accelerates wound healing for DFUs. The mean wound healing time was similar between the stem cell and EGF groups. However, additional reviews of rigorous, large, well-designed RCTs are warranted for further validation of our findings.
Successful Perianal Wound Treatment Using the Fecal Management System
Authors: Yu Yi-Shang , Weng Yu-Tse , Wu Chien-Wei , Tzeng Yuan-Sheng
Published: February 2025

Background

Fecal diversion is important for healing of perianal wounds. However, traditional fecal diversion with colostomy is associated with risks of general anesthesia and requires healthy abdominal skin for stoma creation. Alternative methods of fecal diversion are needed.

Aim and Objectives

We aimed to illustrate an effective alternate method of fecal diversion in patients with perianal wounds by reporting 2 patients with perianal wounds who were successfully treated using the fecal management system.

Materials and Methods

The first patient was a 79-year-old female with a grade IV sacral pressure injury who underwent operative debridements and vacuum-assisted wound closure. The second patient was a 21-year-old female with extensive perianal burn wounds who underwent a series of debridements, wound dressing changes, and split-thickness skin grafts. The fecal management system was utilized for fecal diversion in both patients.

Results

Satisfactory wound healing was achieved in each patient using the fecal management system for fecal diversion.

Conclusions

Based on our 2 patients and previous studies that have reported successful treatment of perianal wounds using the fecal management system, this system is feasible to use and effective. We suggest its use in patients with perianal wounds, particularly those in whom colostomy is not preferable or contraindicated.
Patient-Reported Outcomes and Aesthetic Evaluations in Autologous Breast Reconstruction at Taipei Veterans General Hospital
Authors: Cheng Qi-Rui , Feng Chin-Jung , Hsiao Fu-Yin , Tseng Ling-Ming , Huang Chi-Cheng , Tsai Yi-Fang , Lin Yen-Shu , Wang Shyh-Jen , Yu Wen-Chan , Perng Cherng-Kang
Published: February 2025

Background

Improving the quality of life increases patients' expectations of postmastectomy breast reconstruction. Increased incidence of breast implant-associated anaplastic large cell lymphoma encourages patients to choose autologous breast reconstruction over implantation. This study aimed to analyze the aesthetic outcomes of autologous breast reconstruction and define factors associated with the results.

Methods

We recruited patients for immediate or delayed autologous tissue reconstruction after mastectomy from October 2015 to June 2021 at a single institute in Taiwan. Patient demographic data, operative complications, and secondary cosmetic revisions were identified through a medical chart review. Patient-reported outcomes (PROs) and perioperative imaging records were analyzed using the BREAST-Q questionnaire and Breast Cancer Conservation Treatment (BCCT).core, respectively, for aesthetic outcome evaluations.

Results

Eighty-three women were enrolled, with a 73% BREAST-Q questionnaire response rate, and followed-up for a mean 36 (6–78) months. The mean BREAST-Q score for satisfaction with breasts was 60.46 (standard deviation = 19.09). The postoperative BCCT.core evaluation did not differ significantly from the preoperative evaluation (P = 0.245), and most patients (70.59%) reported similar (50%) or better results (20.59%) after reconstruction. Postmastectomy radiotherapy impacted negatively on psychosocial well-being (P = 0.012), sexual well-being (P = 0.002), and satisfaction with breast (P = 0.026). Three-dimensional breast molds might improve psychosocial well-being BREAST-Q scores, sexual well-being, and breast satisfaction but was not statistically significant.

Conclusions

Breast reconstruction with autologous tissue had an acceptable complication rate and favorable aesthetic outcomes in PROs and BCCT.core. Postmastectomy radiotherapy resulted in worse PROs and a 3-dimensional breast mold may facilitate better outcomes.
The Seven-Day Method
Authors: Tanaka Eiko , Chuang Andy Deng-Chi , Chiu Wen-Kuan , Tsai Chia-Hsuan
Published: February 2025

Introduction

Aesthetic reduction of the labia minora has increased in popularity over the recent decades. Numerous surgical techniques have surfaced, each with their advantages and shortcomings. Regardless of resection technique, recovery period of up to 6 weeks after labia minora reduction surgery has been recommended.

Method

A modification of the edge resection technique described herein eliminates the need for suture removal and allows for expedited recovery within a week. Patients receiving the eponymously named seven-day method at a single aesthetic center were evaluated for aesthetic outcome, complications, reoperation rate, and overall patient satisfaction.

Results

Of the 80 patients surveyed, aesthetic outcome and patient satisfaction were either “satisfied” or “very satisfied” in 96.9% and 87.5% of the patients, with a mean score of 4.6 and 4.2 out of 5, respectively. Complications included bleeding, uneven contour, dehiscence, swelling, stitch exposure, pain, and itching. Overall reoperation rate was 3.8% and were all for elective and aesthetic purposes.

Conclusions

The seven-day method is a relatively simple and undemanding technique that allows quick postoperative recovery without the need for follow-up, promising good patient satisfaction and outcome.
Pseudoalteromonas holothuriae sp. nov., isolated from the sea cucumber Holothuria forskali
Authors: Yvin Marion , Mühle Estelle , Chesneau Olivier , Laguerre Hélène , Brillet Benjamin , Fleury Yannick , Jégou Camille , Kämpfer Peter , Lipski André , Criscuolo Alexis , Clermont Dominique , Le Chevalier Patrick
Published: February 2025

Two motile bacterial strains, designated as cfHf56-1T and SW 252, were isolated from the coelomic fluid of Holothuria forskali and from the surrounding seawater at the animal sampling site, respectively. The sea cucumber was collected in the Glénan archipelago (Brittany, France). Strains cfHf56-1T and SW 252 were Gram-stain-negative, non-spore-forming and rod-shaped bacteria. Colonies made on marine agar plates were brown in color. The pH and temperature ranges for growth were 7–8 and 18–30 °C, respectively, in marine broth. The major fatty acids were 16 : 1 cis9 and 16 : 0. Phylogenetic analyses evidenced that both strains belong to a novel species in the genus Pseudoalteromonas. The strains were closely related to the type strains of Pseudoalteromonas caenipelagi, Pseudoalteromonas byunsanensis and Pseudoalteromonas amylolytica, with 75–78 % ANI and 19–21 % dDDH values. In this context, cfHf56-1T (= CIP 111854T = CECT 30642T) is considered as the type strain of the novel species for which the name Pseudoalteromonas holothuriae sp. nov. is proposed. The genome of the type strain is characterized by a size of 5.1 Mbp and a G+C content of 40.5%.
Reclassification of Actinomadura catellatispora Lu et al. 2003 as a later synonym of Actinomadura livida Lavrova and Preobrazhenskaya 1975 (Approved List 1980) based on whole-genome analysis
Authors: Dif Guendouz , Djemouai Nadjette , Meklat Atika , Zitouni Abdelghani
Published: February 2025

The genus Actinomadura comprises Gram-positive bacteria found in diverse natural environments and is classified in the family Thermomonosporaceae within the order Streptosporangiales. Some species exhibit considerable phylogenetic and taxonomic overlaps, prompting a comprehensive investigation that integrates phylogenetic, phylogenomic and comparative genomic analyses to elucidate the taxonomic status of two Actinomadura species. Actinomadura livida JCM 3387ᵀ and Actinomadura catellatispora DSM 44772T shared 16S rRNA gene sequence similarity of 99.9% and digital DNA–DNA hybridization values of 99.8%. Moreover, the average nucleotide identity value for the two species was 99.8%, indicating minimal genomic variation between the two strains. Also, the distribution of carbohydrate-active enzymes and biosynthetic gene clusters predicted to code for secondary metabolites between the two species were almost identical. Data of overall genomic similarity support that Actinomadura catellatispora Lu et al. 2003 be a later heterotypic synonym of Actinomadura livida Lavrova and Preobrazhenskaya 1975 (Approved Lists 1980).
MolGene-E: Inverse Molecular Design to Modulate Single Cell Transcriptomics
Authors: Ohlan Rahul , Murugan Raswanth , Xie Li , Mottaqi Mohammedsadeq , Zhang Shuo , Xie Lei
Published: February 2025

Designing drugs that can restore a diseased cell to its healthy state is an emerging approach in systems pharmacology to address medical needs that conventional target-based drug discovery paradigms have failed to meet. Single-cell transcriptomics can comprehensively map the differences between diseased and healthy cellular states, making it a valuable technique for systems pharmacology. However, single-cell omics data is noisy, heterogeneous, scarce, and high-dimensional. As a result, no machine learning methods currently exist to use single-cell omics data to design new drug molecules. We have developed a new deep generative framework named MolGene-E to tackle this challenge. MolGene-E combines two novel models: 1) a cross-modal model that can harmonize and denoise chemical-perturbed bulk and single-cell transcriptomics data, and 2) a contrastive learning-based generative model that can generate new molecules based on the transcriptomics data. MolGene-E consistently outperforms baseline methods in generating high-quality, hit-like molecules from gene expression profiles obtained from single-cell datasets as validated by target knock-out experiments using CRISPR. This superior performance is demonstrated across diversede novomolecule generation metrics. Extensive evaluations demonstrate that MolGene-E achieves state-of-the-art performance for zero-shot molecular generations. This makes MolGene-E a potentially powerful new tool for drug discovery.
Unique Adaptations of a Photosynthetic MicrobeRhodopseudomonas palustristo the Toxicological Effects of Perfluorooctanoic Acid
Authors: Kathol Mark , Azme Anika , Saifur Sumaiya , Aich Nirupam , Saha Rajib
Published: February 2025

In this study, we investigate the PFOA removal capabilities ofRhodopseudomonas palustris(R. palustris), a fluoroacetate dehalogenase containing microbe as a potential candidate for achieving bioremediation. In the 50-day PFOA uptake experiment, R. palustris removed 44 ± 6.34 % PFOA after 20 days of incubation, which was then reduced to a final removal of 6.23 ± 12.75 %. Results indicate PFOA was temporarily incorporated into the cell membrane before being released partially into the media after cell lysis. This incorporation might be attributed to the combined effect of hydrophobic interaction between PFOA and the cell membrane and the reduced electrostatic repulsion from the high ion presence in the growth medium. The growth ofR. palustrisduring the PFOA uptake experiment was 9-fold slower than their growth without PFOA. This study also completely defines the toxicity range of PFOA forR. palustristhrough a toxicity assay. Increasing PFOA concentration reduced the microbe growth, with complete inhibition around 200 ppm. For various concentrations of PFOA, R. palustris exhibits interesting diauxic growth behavior. An accelerated growth phase was followed by a temporary death phase in the first 24 hours in the presence of 12.5-100 ppm PFOA, implying a unique adaptation mechanism to PFOA.
Circularization of Single-Stranded DNA Donor Template Unleashes the Power of Non-Viral Gene Delivery for Long-Term HSCs editing
Authors: Letort Gil , Duclert Aymeric , Clerre Diane Le , Chion-Sotinel Isabelle , Salvatori Roger , Dessez Emilie , Sevin Margaux , Rotondi Marco , Ducani Cosimo , Duchateau Philippe , Valton Julien
Published: February 2025

Over the past decade, non-viral DNA template delivery has been used with engineered nucleases to target single-stranded DNA sequences in hematopoietic stem and progenitor cells. While effective for gene therapy, this method has been limited to short DNA donor templates, restricting its applications to gene corrections. To expand its scope, we developed an editing process using kilobase-long circular single-stranded DNA donor templates and TALEN technology. Our results show that the CssDNA editing process achieves high gene insertion frequency in viable HSPCs. Compared to a conventional AAV-editing process, CssDNA-edited HSPCs show a higher propensity to engraft and maintain gene edits in a murine model. This positive outcome is partly due to higher levels of primitive edited HSPCs, a more quiescent metabolic state, and elevated expression of bone marrow niche adhesion markers. Our findings highlight the strong potential of CssDNA as a universal and efficient non-viral DNA template for gene therapy applications.