bluuebunny/crossref_metadata_2025 huggingface dataset:
Interobserver and Intraobserver Variability in Crural Angiography
Authors: van Wely Chrissy , Oosterveld Rens J. , Zonnebeld Niek , Yazar Ozan , van ’t Hof Arnoud W. J. , Bouwman Lee H.
Published: January 2025

Objective:

The gold standard imaging modality for assessing crural arterial disease is digital subtraction angiography (DSA). Using DSA, the operator can estimate the diameter and degree of stenosis and determine the diameter of the balloon. Since these measures are estimates, it allows for interobserver and intraobserver variability. This study aimed to determine the interobserver and intraobserver variability in the assessment of crural angiography.

Method:

A total of 15 angiographies with corresponding patient characteristics were presented to 7 assessors, including 3 vascular surgery residents and 4 vascular surgeons on 3 separate occasions. A series of questions was presented, including vessel identification, estimated diameter, estimated degree of stenosis, treatment decision, and which type of balloon or stent would be used including diameter. The primary outcomes were interobserver and intraobserver variability in the estimated diameter of the artery, the estimated degree of stenosis and treatment decision. Secondary outcomes were vessel identification and how the lesion would be treated. Interobserver and intraobserver agreement was calculated using intraclass correlation coefficients (ICCs) and Hubert’s kappa, interpreted as poor (<.50), moderate (.50–.75), good (.75–.90), and excellent (>.90) agreement.

Results:

Interobserver agreement was moderate (.62) for estimated vessel diameter, moderate (.72) for degree of stenosis and moderate (.53) for whether the physician would treat the stenosis. The interobserver agreement was poor regarding balloon diameter (.21). The intraobserver agreement ranged from moderate to good (.62-.80) for estimated vessel diameter and was good for estimated degree of stenosis (.76-.87). The intraobserver agreement regarding treatment decision ranged from moderate to excellent (.76-.87) and ranged from poor to moderate (.07-.57) for balloon diameter.

Conclusion:

This study shows moderate interobserver agreement and moderate to good intraobserver agreement regarding estimated vessel diameter. In addition, moderate to excellent intraobserver agreement and moderate interobserver agreement regarding treatment decision was found. This study also showed poor to moderate agreement, both interobserver and intraobserver, regarding balloon sizing. There is a need for more objective diagnostic modalities to assess the diameter and morphology of crural lesions.

Clinical Impact

Digital subtraction angiography (DSA) is currently the golden standard imaging modality guiding below-the-knee percutaneous transluminal angioplasty (PTA). Due to the lack of objective measurements with DSA, physicians estimate vessel diameter and percentage of stenosis. The present study shows that there is inter- and intraobserver variability in the assessment of DSA, indicating there is a need for objective imaging modalities guiding below-the-knee PTA.
Apple Vision Pro-guided Laparoscopic Radio Frequency Ablation for Liver Tumors: The Pioneer Experience
Authors: Tsai Yu-Chieh , Hsiao Chin-Cheng , Chung-Wei Lin Charles , Chern Ming-Chih , Huang Shih-Wei
Published: January 2025

Background: This study evaluates the feasibility of Apple Vision Pro goggles as an augmented reality (AR) surgical navigation tool for laparoscopic-assisted ultrasound-guided radiofrequency ablation (RFA) of liver tumors. Traditional RFA is effective but challenging due to the integration of multiple imaging modalities.

Purpose: The primary aim of this research is to assess how Vision Pro goggles can enhance the surgical navigation process during RFA, improving tumor localization and the overall effectiveness of the procedure.

Research Design: A feasibility study design was used to analyze the implementation of AR technologies in surgical navigation, focusing specifically on their application in laparoscopic surgeries.

Study Sample: Participants included patients undergoing laparoscopic-assisted ultrasound-guided RFA, with pre-operative imaging workups involving CT and MRI scans followed by intraoperative laparoscopic sonography.

Data Collection and/or Analysis: Data were collected through observations during surgical procedures using the Vision Pro goggles, which displayed various imaging inputs (MRI, 3D reconstruction, and laparoscopic sonography) in the surgeon's field of view. Image manipulation was assessed based on accuracy and effectiveness of tumor ablation.

Results: The goggles enhanced tumor localization accuracy and facilitated real-time image manipulation, resulting in effective tumor ablation. Initial results show promising outcomes in the precision and efficiency of the RFA procedure.

Conclusions: While the initial results are promising, larger studies are necessary to validate the technology's efficacy and safety. Future research should compare outcomes with traditional methods and explore its applicability to other surgeries, aiming to refine the system further. The Vision Pro goggles potentially represent a significant advancement in surgical technology by improving RFA precision and efficiency.
Outcomes of Suction Debulking and Surgery in Patients With Isolated Tricuspid Valve Endocarditis
Authors: Modi Roshan D. , Ueyama Hiroki A. , Tully Andy , Byku Isida , Greenbaum Adam B. , Xie Joe X. , Gleason Patrick T. , Daneshmand Mani , Babaliaros Vasilis C. , Keeling Brent
Published: January 2025

Objective:

Percutaneous vegetation debulking has been reported to treat tricuspid valve infective endocarditis (TVIE), but data on feasibility compared with conventional surgical strategies are limited. We aimed to compare short-term outcomes of suction debulking with partial venovenous bypass to conventional open surgery in this population.

Methods:

This was a single-center, retrospective study that included all patients with isolated TVIE who underwent suction debulking with partial venovenous bypass or tricuspid valve surgery between January 2010 and December 2022. Patient characteristics, procedural data, and clinical outcomes were compared.

Results:

Of the 45 patients included, 16 (35.6%) underwent suction debulking and the remainder (64.4%) underwent surgery. Baseline characteristics were comparable, including high rates of preprocedure hemodialysis (11.1%), prior infectious endocarditis (44.4%), intravenous drug use (60.0%), presence of tricuspid bioprostheses (24.4%), and septic shock (40.0%). Suction debulking had a shorter procedure time than surgery (206 [176 to 224] min vs 400 [325 to 487] min, P < 0.001) and was associated with numerically lower rates of various complications including acute kidney injury requiring hemodialysis, limb ischemia, and dysrhythmia requiring pacemaker. Over a mean follow-up period of 473 ± 604 days, recurrent endocarditis (37.5% vs 17.2%, P = 0.25) and the need for reintervention (50.0% vs 17.2%, P = 0.048) were higher with suction debulking. However, all-cause mortality was similar between the groups (12.5% vs 10.3%, P > 0.99).

Conclusions:

Suction debulking can safely be performed in patients with isolated TVIE with shorter procedural times and similar midterm all-cause mortality compared with surgery. Suction debulking may be appropriate initial therapy for this complex population.
Arthroscopic treatment of scaphoid nonunion with debridement and cancellous bone grafting before or after K-wire fixation
Authors: Quemener–Tanguy Alexandre , Vigié Rémy , Koelhy Axel , Ballet Safire , De Villeneuve Bargemon Jean-Baptiste , Levadoux Michel
Published: January 2025

We compared the outcomes of two groups of patients with scaphoid nonunion treated with arthroscopic cancellous bone grafting. In group 1, K-wires were introduced beforehand and in group 2 after debridement and packing bone grafts in the nonunion site. Our hypothesis was that the percentage of unions would be higher in group 2. We conducted a retrospective, single-centre comparative study of two consecutive series of patients. Seventeen patients in group 1 were operated between 2011 and 2015 and 25 patients in group 2 between 2015 and 2022. At 3 months, there was already a significant difference in consolidation, with three fractures united in group 1 and 21 in group 2. At 6 months, 10 patients (59%) united in group 1 and 24 (96%) in group 2. Debridement of the nonunion site without K-wires in place may allow a more thorough debridement and extensive filling of the defect with bone graft. If an arthroscopic technique is used for scaphoid nonunion, we do not recommend prior fixation with K-wires.

Level of evidence: III
Arthroscopic foveal reattachment of triangular fibrocartilage complex: Inside-out technique at specific ulnocarpal anatomical landmarks
Authors: Waitayawinyu Thanapong , Kanjanapirom Patipan , Siritattamrong Pitchapa , Boonyasirikool Chinnakart , Niempoog Sunyarn
Published: January 2025

This study evaluates the outcomes of arthroscopic triangular fibrocartilage complex (TFCC) foveal reattachment using an inside-out suture passing through the TFCC at specific ulnocarpal anatomical landmarks to grasp the radioulnar ligaments. Thirty-eight patients with a mean age of 36 years (range 19–54), diagnosed with TFCC injury with distal radioulnar joint (DRUJ) instability, underwent arthroscopic inside-out TFCC foveal reattachment using designated suture sites. At a mean follow-up of 32 months (range 26–44), pain score, range of motion, grip strength, Disabilities of the Arm, Shoulder and Hand (DASH) score, and Modified Mayo Wrist Score all showed significant improvement after surgery. The DRUJ stability was restored and the minimal clinically important difference threshold for the DASH score was achieved in all patients. Arthroscopic TFCC foveal reattachment using the inside-out technique at specific ulnocarpal anatomical landmarks provided reliable outcomes and could be considered as another straightforward procedure for treating TFCC injuries with DRUJ instability.

Level of evidence: IV
Guideline on managing thumb base osteoarthritis: The British Society for Surgery of the Hand Evidence for Surgical Treatment (BEST) findings and recommendations
Authors: Gangopadhyay Soham , Jansen Victoria , Sim Khor Wee , Gardiner Matthew D. , Burchette Daniel , McKenna Helen
Published: January 2025

This review paper provides a summary of the evidence for non-surgical and surgical management of thumb base osteoarthritis and suggests guidelines through Clinical Practice Recommendations including Good Practice Points and a Patient Flow Algorithm. The guidelines were developed through systematic reviews in accordance with the British Society for Surgery of the Hand Evidence for Surgical Treatment (BEST) Process Manual, which has been accredited by the National Institute for Health and Care Excellence. A stepwise approach is recommended with initial non-invasive treatment consisting of a comprehensive and multimodal package of supported self-management. Splints should be additionally considered for those who have not responded to a self-management package alone. Intra-articular corticosteroid injections should be considered in those who have not responded to non-invasive treatment. If symptoms fail to resolve, surgery should be considered. Additional procedures such as interposition or ligament reconstruction do not appear to confer any benefit over excision of the trapezium alone.
Novel approach for noninvasive pelvic floor muscle strength measurement using extracorporeal surface perineal pressure measurement and machine learning modeling
Authors: Hwang Ui-jae , Ahn Sun-hee , Lee Hyeon-ju , Jeon Yurin , Jeon Myung Jae
Published: January 2025

Objective

Accurate measurement of pelvic floor muscle (PFM) strength is crucial for the management of pelvic floor disorders. However, the current methods are invasive, uncomfortable, and lack standardization. This study aimed to introduce a novel noninvasive approach for precise PFM strength quantification by leveraging extracorporeal surface perineal pressure (ESPP) measurements and machine learning algorithms.

Methods

Twenty-one healthy women participated in this study. ESPP measurements were obtained using a 10 × 10 pressure array sensor during maximal voluntary PFM contractions in a seated position. Simultaneously, transabdominal ultrasound was used to measure bladder base displacement (mm) as a reference for PFM contraction strength. Seven ESPP variables were calculated based on ESPP data and intra- and inter-rater reliabilities were assessed. Machine learning algorithms predicted bladder base displacement from ESPP variables.

Results

The ESPP measurements demonstrated good to excellent intra-rater (ICC = 0.881) and inter-rater (ICC = 0.967) reliability. Significant correlations were observed between bladder base displacement and middle ( r = .619, P < .001) and front ( r = −.379, P =.002) vectors. The top-performing models for predicting bladder base displacement were the support vector machine [root mean square error (RMSE) = 0.139, R2 = 0.542], random forest (RMSE = 0.123, R2 = 0.367), and AdaBoost (RMSE = 0.123, R2 = 0.320) on the training set, and AdaBoost (RMSE = 0.173, R2 = 0.537), random forest (RMSE = 0.177, R2 = 0.512), and support vector machine (RMSE = 0.178, R2 = 0.508) on the test set. In predicting bladder base displacement, Bland–Altman analysis revealed these models had minimal systematic bias, with mean differences ranging from −0.007 to 0.066, and clinically acceptable limits of agreement.

Conclusion

This study demonstrates the potential of ESPP measurements and machine learning algorithms as a reliable and valid noninvasive approach for assessing PFM strength by quantifying the directionality of contractions, overcoming the limitations of traditional techniques.
Renal thrombotic microangiopathy from Bevacizumab treated with Eculizumab: A case report
Authors: Fardi Yasameen , Grosser Daniel , Rashidi Arash
Published: January 2025

We present a case of a 76 year old female with biopsy proven thrombotic microangiopathy secondary to Bevacizumab, who was treated with Eculizumab. She had a history of hepatocellular carcinoma that was treated with Atezolizumab and Bevacizumab. She presented to the hospital for peripheral edema and confusion with workup significant for acute kidney injury and proteinuria. Renal biopsy revealed findings consistent with thrombotic microangiopathy. Her renal function continued to worsen eventually requiring hemodialysis.

Bevacizumab is a vascular endothelial growth factor (VEGF) targeting monoclonal antibody that is associated with hypertension, proteinuria, and renal thrombotic microangiopathy (TMA). Pathophysiology of injury includes direct endothelial cell injury and initial treatment is drug discontinuation. Our patient presented with worsening acute kidney injury (AKI) despite receiving her last dose of Bevacizumab 1 month prior. For this reason, therapy with Eculizumab was started and she received a total of four doses with outcome of improved urine output and stabilization of serum creatinine off of dialysis. This case suggests further therapeutic role of Eculizumab for Bevacizumab associated TMA.
Audit of B-cell Cancer Genes
Authors: Coyle Krysta Mila , Dreval Kostiantyn , Hodson Daniel J , Morin Ryan D
Published: January 2025

Comprehensive genetic analysis of tumors with exome or whole genome sequencing has enabled the identification of the genes that are recurrently mutated in cancer. This has stimulated a series of exciting advances over the past 15 years, guiding us to new molecular biomarkers and therapeutic targets among the common mature B-cell neoplasms. In particular, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Burkitt lymphoma (BL) have each been the subject of considerable attention in this field. Currently, more than 850 genes have been reported as targets of protein-coding mutations in at least one of these entities. To reduce this to a manageable size, we describe a systematic approach to prioritize and categorize these genes, based on the quality and type of supporting data. For each entity, we provide a list of candidate driver genes categorized into Tier 1 (high-confidence genes), Tier 2 (candidate driver genes), or Tier 3 (lowest-confidence genes). Collectively, this reduces the number of high-confidence genes for these three lymphomas to a mere 144. This further affirms the substantial overlap between the genes relevant in DLBCL and each of FL and BL. These highly curated and annotated gene lists will continue to be maintained as a resource to the community. These results emphasize the extent of the knowledge gap regarding the role of each of these genes in lymphomagenesis. We offer our perspective on how to accelerate the experimental confirmation of drivers using a variety of model systems, using these lists as a guide for prioritizing genes.
Systemic Mastocytosis: Current Status and Challenges in 2024
Authors: Ustun Celalettin , Keklik Karadag Fatma , Linden Michael A , Valent Peter , Akin Cem
Published: January 2025

Systemic mastocytosis (SM) is a rare disease and has had significant discoveries in its biology, prognostication, and management in the past two decades. The latest update of the WHO classification and the new ICC classification are current standards in the diagnosis and prognostication of SM. In clinical practice, SM can be divided into two main categories: non-advanced SM (nonAdvSM) and advanced SM (AdvSM). The integration of clinical signs and symptoms as well as bone marrow morphologic, immunophenotypic, and molecular results is required to diagnose SM variants. In the modern era, data with KIT inhibitors (i.e., avapritinib) suggest prolongation of survival in AdvSM. Although this is encouraging progress, and we now have effective drugs for managing both ISM and AdvSM patients, there are still remaining challenges in SM. For example, optimal initial treatment in certain patient subsets, such as SM with an associated hematologic neoplasm (SM-AHN), remains under debate (e.g., treatments targeting AHN or SM, monotherapy or combinations). Prospective studies evaluating drugs with different mechanisms of action are needed for such patients. This review provides an updated overview of SM, including the latest methods for diagnosis, patient classification based on their prognosis, and management according to the most significant clinical trials, covering both patients with nonadvSM and AdvSM.
Nivolumab and rituximab in treatment naive follicular lymphoma: the phase II '1st FLOR' study
Authors: Barraclough Allison , Lee Sze Ting , Burgess Melinda , Churilov Leonid , Chong Geoffrey , Lee Denise , Gilbertson Michael , Fancourt Tineke , Manos Kate , Ritchie David , Koldej Rachel M , Scott Andrew , Keane Colm , Hawkes Eliza A
Published: January 2025

Follicular lymphoma (FL) outcomes are heavily influenced by host immune activity with immune anti-tumor activity mitigated by PD-1/PD-L1 pathway engagement. Combination CD20-directed therapy plus PD-1 inhibition (PD-1i) increases T-cell tumor killing and NK-cell antibody-dependent cell cytotoxicity (ADCC). Mounting evidence supports immune-priming using PD-1i before cancer-directed agents. Our multicentre, open-label, phase II 1st FLOR study (NCT03245021) enrolled 39 previously-untreated advanced-stage FL patients to receive 4 cycles of nivolumab (240mg) then 4 cycles of 2-weekly nivolumab plus rituximab 375mg/m2 (induction) then 1 year of monthly nivolumab (480mg) plus 2 years of 2-monthly rituximab maintenance. Participants with complete response (CR) after nivolumab priming continued nivolumab monotherapy. The primary endpoint was toxicity during induction. Adverse events (AEs) ≥ grade 3 during induction occurred in 33% (n=13); most commonly elevated amylase/lipase (15%), liver enzyme derangement (11%) and infection (10%). Three patients discontinued nivolumab secondary to toxicity; two pancreatitis, one acute kidney injury. Overall response rate (ORR) was 92% (CR 59%). Median follow-up was 51 months. Median and 4-year progression-free survival (PFS) were 61 months (95%CI 2-72) and 58% (95%CI 34-97); 70% of responders remained in CR. 4-year overall survival was 95%. High baseline total metabolic tumor volume and total lesion glycolysis conferred inferior PFS (p=0.04 and p=0.02). Additionally, high baseline tumor CD8A gene expression was associated with improved PFS (p=0.03). Nivolumab priming followed by nivolumab-rituximab in treatment-naive FL is associated with favorable toxicity and high response rates potentially providing an alternative to chemotherapy. TMTV and high tumor CD8A expression are promising immunotherapy biomarkers for FL.
Elucidation of delignification promotion mechanism by soda cooking with addition of anthraquinone derivative using phenolic β-O-4-type lignin model oligomer
Authors: Luo Ke , Nishimoto Taiki , Matsushita Yasuyuki
Published: January 2025

Using an artificial lignin model oligomer containing only the β-O-4 substructure, we investigated the mechanism, whereby the addition of an anthraquinone derivative (2-ethylanthraquinone; 2-EAQ) promotes pulping during alkaline cooking. Heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) analysis of the reaction products after cooking revealed that an enol ether signal appeared in the spectrum of the product without 2-EAQ, whereas it was not detected in the product with 2-EAQ. This result implies that the reduced type of 2-EAQ (2-ethylanthrahydroquinone, 2-EAHQ) attacked the lignin model oligomer, which promoted β-ether cleavage during soda cooking and reduced the elimination of γ-OH to form enol ether. When 2-EAQ was added, coniferyl alcohol was detected in the black liquor, confirming the reductive degradation of the lignin model oligomer by 2-EAHQ. Surprisingly, the degradation of the lignin model oligomers was accelerated, even in the absence of carbohydrates. Vanillic acid (VA) and ferulic acid (FA) were detected in the degradation products of the lignin model oligomer, suggesting that 2-EAQ oxidized not only the carbohydrates but also the degradation products to form 2-EAHQ.
Trait mindfulness in early pregnancy and adverse perinatal outcomes: a prospective cohort study
Authors: Fain Audra C. , Cersonsky Tess E. K. , Bublitz Margaret H. , Lewkowitz Adam K. , Werner Erika F. , Miller Emily S. , Ayala Nina K.
Published: January 2025

Background

Mindfulness centered therapy has been shown to improve perinatal mental health outcomes. There is emerging evidence that mindfulness training (MT) can also be harnessed to improve somatic outcomes. Yet, little is known about which perinatal populations might benefit the most from mindfulness training interventions. We aimed to evaluate the association between trait mindfulness and adverse pregnancy outcomes.

Methods

This is a planned secondary analysis of a prospective cohort study of nulliparous participants recruited between May 2019 and February 2022 from a single, high volume tertiary care center. Participants completed the validated Mindfulness and Attentive Awareness Scale prior to 20 weeks gestation. Trained research staff abstracted pregnancy and delivery data. The primary outcome was unplanned cesarean delivery (CD). Secondary outcomes included gestational diabetes, hypertensive disorders of pregnancy and a neonatal morbidity composite. We examined outcomes by mindfulness quartile (Q), adjusting for covariates determined a priori.

Results

Of the 281 participants with full outcome data, 47.9% experienced one or more of the adverse perinatal outcomes and the median trait mindfulness score was 4.6 (IQR 3.9–5.3). After adjusting for potential confounders, there were significantly lower rates of CD rates in those in Q2 and Q3 compared to Q4 (adjusted odds ratio [aOR] Q2 0.42, 95% confidence interval [CI] 0.20 – 0.87, Q3 aOR 0.23, 95% CI 0.10–0.51). There were no differences in rates of gestational diabetes, hypertension or composite neonatal outcomes by trait mindfulness quartile.

Conclusions

In this prospective cohort of nulliparous people, those with trait mindfulness in the 2nd and 3rd quartiles had lower rates of CD. Given prior literature suggesting active MT decreases adverse outcomes, there may be a component of the active practice of mindfulness, rather than trait mindfulness levels, associated with improved outcomes.
Effects of physical activity on depressive and anxiety symptoms of women in the menopausal transition and menopause: a comprehensive systematic review and meta-analysis of randomized controlled trials
Authors: Yue Hongyu , Yang Yijiao , Xie Fangfang , Cui Jiahe , Li Yang , Si Mengran , Li Shanshan , Yao Fei
Published: January 2025

Background

Depression and anxiety may significantly affect women in the menopausal transition and menopause. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, physical activity (PA) have been increasingly studied, but there is no consensus about their role in menopausal women with depression and anxiety.

Objective

The current study aimed to evaluate the effect of PA on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition and menopause.

Methods

We searched for relevant published studies in PubMed, Embase, Web of Science, Cochrane Library, and CINAHL prior to 8 April 2024, focusing on randomized controlled trials documenting the effect of physical activity on DS and AS, and assessed study quality using the Newcastle–Ottawa Scale.

Results

The data used for meta-analysis were derived from 21 studies (DS, n = 9; AS, n = 1; DS and AS combined, n = 11) involving 2020 participants. The results showed that PA groups demonstrated a statistically significant effect of depressive symptoms versus controls (DS [SMD: -0.66, 95% CI: -0.99 to -0.33; P < 0.001]; AS [SMD: -0.55, 95% CI: -0.82 to -0.27; P < 0.001]). As subgroup analyses demonstrated, physical exercise also reduced depressive symptom of women in menopausal status (SMD =-0.56, 95% CI: −0.96 to − 0.17, p = 0.006, I2 = 69%), postmenopausal status (SMD =-0.94, 95% CI: −1.46 to − 0.42, p = 0.0004, I2 = 94%), and both in menopausal transition and postmenopausal status (SMD =-0.30, 95% CI: −0.49 to − 0.12, p = 0.001, I2 = 0%), while it only reduced anxiety symptom of postmenopausal women (SMD =-0.96, 95% CI: −1.49 to − 0.43, p = 0.0004, I2 = 89%). Low-intensity and moderate-intensity exercise both produced increasingly benefits over depressive and anxiety symptoms. However, there is no statistically significant effect of exercise intensity on both depressive symptom and anxiety symptom.

Conclusion

Physical activities with low to moderate intensity can impart remarkable improvements for managing menopausal women with depression and anxiety.
High clinical burden of classical homocystinuria in the United States: a retrospective analysis
Authors: Jain Mahim , Shah Mehul , Thakker Kamlesh M. , Rava Andrew , Pelts Block Agnes , Ndiba-Markey Colette , Pinto Lionel
Published: January 2025

Background

Classical homocystinuria (HCU) is a rare genetic metabolic disorder resulting in elevated homocysteine and methionine levels. The clinical characteristics and associated complications of HCU are well documented. However, there is limited published research on the clinical burden of patients with HCU, especially stratified by total homocysteine (tHcy) levels. This study aimed to describe the overall clinical burden of patients with HCU in the United States and key clinical events by tHcy levels using administrative claims data.

Methods

This non-interventional retrospective cohort analysis from January 01, 2016, through September 30, 2021, used Optum’s de-identified Market Clarity Data. Patients who had 1 or more International Classification of Diseases, Tenth Revision code for homocystinuria (E72.11) or the signs, disease, and symptoms term homocystinuria in the natural language processing dataset were included. To obtain a study population most likely to have HCU, stratifications by tHcy levels, clinical characteristics, and phenotypic expressions were applied to refine the cohort. Included patients were then stratified by highest tHcy level. Clinical burden was measured by category of HCU-related events. Descriptive statistics were reported.

Results

Six hundred thirty-three patients met the inclusion criteria, and 601 patients had a tHcy level: < 50 µM (n = 278), 50 to < 100 µM (n = 212), and ≥ 100 µM (n = 111). Among the 601 patients with a tHcy level, almost one-half (n = 297, 49.4%) had at least one thrombotic/thromboembolic, skeletal, ocular, or neurological event and 14.1% (n = 85) had multiple events. Thrombotic/thromboembolic events (n = 186, 30.9%) were the most common type of events, followed by skeletal (n = 100, 16.6%), ocular (n = 63, 10.5%), and neurological events (n = 50, 8.3%). During follow-up, 5.7% (n = 34) of the patients died. All events assessed were more prevalent in the 50 to < 100 µM group and ≥ 100 µM group compared with those in the < 50 µM group.

Conclusions

As has been believed, patients with tHcy ≥ 100 µM carried a substantial clinical burden, but the burden is also very high in those whose levels were ≥ 50 µM. Thrombotic/thromboembolic events were more common than skeletal, ocular, or neurological events. Meaningfully lowered tHcy levels may help to reduce significant clinical events.
Combined biochemical profiling and DNA sequencing in the expanded newborn screening for inherited metabolic diseases: the experience in an Italian reference center
Authors: Fecarotta Simona , Vaccaro Lorenzo , Verde Alessandra , Alagia Marianna , Rossi Alessandro , Colantuono Chiara , Cacciapuoti Maria Teresa , Annunziata Patrizia , Riccardo Sara , Grimaldi Antonio , Fusco Tonya , De Santis Rosa , Barretta Fernando , Albano Lucia , Crisci Daniela , Vallone Fabiana , Tarallo Antonietta , Cesana Marcella , Brunetti-Pierri Nicola , Frisso Giulia , Ruoppolo Margherita , Cacchiarelli Davide , Parenti Giancarlo
Published: January 2025

Background

Newborn screening (NBS) programs have significantly improved the health and outcomes of patients with inherited metabolic disorders (IMDs). Methods based on liquid chromatography/mass spectrometry (LC–MS/MS) analysis are viewed worldwide as the gold standard procedure for the expanded NBS programs for these disorders. Advanced molecular technologies point to genomic sequencing as an alternative and feasible strategy for the screening of genetic diseases, including IMDs. However, each of the two approaches has potential limitations when used as a first-tier analysis. In this study, we tested a workflow-based parallel biochemical and sequencing analyses to determine whether this approach could improve the diagnostic outcome.

Results

For each patient identified by LC–MS/MS as positive, we performed both the biochemical confirmatory tests and next-generation sequencing (NGS) procedures from the same Dried Blood Spot (DBS). NGS analysis was based on applying Exome Sequencing libraries, limiting the analysis to 105 actionable genes involved in IMDs. This allows overtaking the actual limitations of NBS on DBS, enhancing our capacity to identify variants that can drive a genetic disease. Through this approach, we could reach 100% of cases solved, with 37.9% of cases (41/108) for which the combination of the biochemical and NGS analysis was indispensable for a correct diagnosis. In total, we could identify 17 affected, 34 false positives, 12 individuals referred to us for maternal conditions. In 45 newborns the molecular analysis showed heterozygosity for mutations in one or more of the genes analyzed, with results compatible with the biochemical profile indicative of NBS positivity.

Conclusions

In this study, we validated the performance of the proposed workflow. The advantage of this approach is limiting molecular analysis only to positive newborns and using a restricted panel of 105 genes relevant for the expanded NBS, with a 100% rate of diagnosis and potential reduction of the costs related to NBS procedures and reduced impact on patients and families.
Salivary gland stem/progenitor cells: advancing from basic science to clinical applications
Authors: Langthasa Jimpi , Guan Li , Jinagal Shyam Lal , Le Quynh-Thu
Published: January 2025

Salivary gland stem/progenitor cells (SSPCs) hold significant potential for regenerative medicine, especially for patients suffering from salivary gland dysfunction due to various causes such as radiation therapy, Sjögren’s syndrome, and aging. This review provides a comprehensive overview of SSPCs, including their characteristics, isolation, culture techniques, differentiation pathways, and their role in tissue regeneration. Additionally, we highlight recent advances in cell- and tissue-based therapies, such as SSPC transplantation and bioengineered organ replacements. The challenges in translating SSPC research into effective clinical therapies are also discussed, alongside proposed solutions and future research directions.
Modeling precaution, immunity loss and dispersal on disease dynamics: a two-patch SIRS model
Authors: Sun Guowei , Mai Ali , Jin Zhen
Published: January 2025

An SIRS model is developed to account for precautionary measures and immunity loss. The existence and stability of equilibria are studied. It is shown that precautionary measures can induce Hopf bifurcations leading to the occurrence of cyclical behavior. The model is then extended to a two-patch scenario to explore how disease spread patterns are influenced by dispersal (travel). Theoretical analyses establish the stability of the disease-free equilibrium, the basic reproduction number, and thresholds related to travel rates. The persistence of the system, as well as the existence of boundary and endemic equilibria, are also discussed. Using Hopf bifurcation theory, we further examine the interaction between nonlinear incidence functions, travel rates, and precaution delay effects in shaping the stability of the endemic equilibrium. The findings reveal a strong connection between reduced infection rates due to precaution and the emergence of Hopf bifurcations, emphasizing the importance of timely and accurate disease information in curbing the spread of diseases. Additionally, the study highlights the significant impact of different infection force functions on equilibrium stability, underscoring the critical role of precautionary measures in disease transmission mechanisms. The results also show the diverse effects of travel rates on disease spread, suggesting that restricting travel may not always lead to favorable outcomes. This underscores the necessity for governments to consider multiple factors comprehensively in their efforts to prevent and control diseases.
Structural basis of FpGalNase and its combination with FpGalNAcDeAc for efficient A-to-O blood group conversion
Authors: Zhou Meiling , Luo Kaishan , Su Chao , Sun Yan , Huang Zuyan , Ma Shuo , Gao Xun , Wang Jiwei , Zhang Chen , Han Pengcheng , Wu Guoqiu
Published: January 2025

Transfusion safety and blood typing continue to present significant challenges in clinical practice, including risks of incorrect blood transfusions and blood shortages. One promising solution is the enzymatic conversion of all red blood cell (RBC) types into universal O-type RBCs. However, the major obstacle to this strategy is the relatively low catalytic efficiency of the enzymes involved. In this study, we investigated two enzymes from Flavonifractor plautii, N-acetylgalactosamine deacetylase (FpGalNAcDeAc) and galactosaminidase (FpGalNase), which demonstrate synergistic activity in efficiently converting A-type RBCs to O-type. We optimized treatment conditions, achieving over 99% conversion in just five minutes using phosphate buffer saline and a 16 nM enzyme concentration. Additionally, we engineered two fusion proteins, FpGalNAcDeAc-FpGalNase and FpGalNase-FpGalNAcDeAc, which showed a 28-fold increase in catalytic efficiency compared to the enzyme mixture. Using cryo-electron microscopy, we resolved the full-length structure of FpGalNase, identifying critical active site residues involved in its catalytic mechanism. This study provides essential structural and biochemical insights for clinical applications in blood group conversion, offering a promising approach for producing universal O-type RBCs.
Learning from the community: iterative co-production of a programme to support the development of attention, regulation and thinking skills in toddlers at elevated likelihood of autism or ADHD
Authors: Hendry Alexandra , Hulks Victoria , Murphy Shona , Radford Holly , Smith Sally , Charman Tony , Mathers Sandra , Rhodes Sinead , Scerif Gaia
Published: January 2025

Programmes designed to support children with known, or increased likelihood of, autism or ADHD often focus on reducing behaviours central to a clinical diagnosis. However, supporting children to pursue their own goals and cope with everyday life through fostering executive function (EF) development, without enforcing neuro-normative assumptions, may be more acceptable to neurodivergent people, and more beneficial. The co-production process for this neurodiversity-affirming programme involved: Review of research priorities identified during published public-and-clinician consultations; iterative programme development through two pilot rounds with a general community sample; and consultation with stakeholders (parents with a connection to autism or ADHD, alongside early years specialists, psychologists and therapists) to check acceptability of the proposal, and refine the logic model and materials. The logic model for the resultant programme—Supporting Toddlers with a connection to autism or ADHD to develop strong Attention, Regulation and Thinking skills (START)—involves three mechanisms of change: The child has appropriate play-based opportunities to practise EF skills; Parenting behaviours linked to strong EFs are encouraged; Parents are empowered to improve environmental-fit for their child so that EF stressors are reduced.
Assessment of flavivirus RNA stability and infectivity in various water environments
Authors: Sano Yuka , Al-Alawi Hawraa , Himeno Misao , Majima Ryuichi , Haga Kazumi , Kyaw Myo Thura , Taniguchi Satoshi , Moi Meng Ling
Published: January 2025

Introduction

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), and Yellow fever virus (YFV) are mosquito-borne RNA viruses causing major public health threats in major parts of the world. While DENV and ZIKV have been detected in urine samples, data on the presence and stability of flaviviruses in the water environment are limited.

Methods

In this study, we determined the stability and infectivity of flavivirus in different water environments by utilizing RT-qPCR and plaque assay to explore the feasibility of environmental detection and surveillance of flaviviruses.

Results

Viral RNA could be detected for up to 49-days, at 4 °C, 25 °C and 37 °C temperatures, and infectious particles could be detected for up to 7 days. While our findings showed that flaviviral RNA has higher stability and better detection rates at lower temperatures, the infectious capacity of flaviviruses was comparatively short at 7 days.

Conclusions

Our results indicate that flaviviruses retains limited infectivity in general water environments and highlight the feasibility of detection and surveillance in various epidemiologic and environmental settings.
Development of the PRECIOUS Short-Form (PRECIOUS-SF) quality of care measure for children with serious illnesses
Authors: Ang Felicia Jia Ler , Cheung Yin Bun , Gandhi Mihir , Malhotra Rahul , Ostbye Truls , Malhotra Chetna , Chow Cristelle Chu-Tian , Chong Poh Heng , Amin Zubair , Tan Teresa Shu Zhen , Finkelstein Eric
Published: January 2025

Background

Rising number of children with complex medical conditions necessitate regular healthcare quality evaluation to achieve optimal outcomes. To address the need for a periodic and quick assessment of quality of care in serious childhood illnesses, we developed a short version of previously validated 45-item PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS) measure.

Methodology

PRECIOUS was administered by parents of children living with serious illnesses at two time-points (baseline and two weeks) in an online survey. PRECIOUS Short-Form (PRECIOUS-SF) items were derived from the full PRECIOUS measure, which comprises five scales, using an exploratory factor analysis and best subset regression. The measurement properties of PRECIOUS-SF scales were assessed using the concurrent validity using Pearson correlation (r) with the PRECIOUS scales, internal consistency (Cronbach’s α) within each scale, convergent validity with overall QoC rating, and test-retest reliability (intraclass correlation coefficient, ICC) between baseline and two-week responses.

Results

PRECIOUS-SF included 10 items across four scales – (1) access to financial and medical resources (2), collaborative and goal-concordant care (3), caregiver support and respectful care and (4) reduction of caregiving stressors. A fifth and optional scale was suggested for hospitalization-specific processes. PRECIOUS-SF scales correlated strongly with corresponding PRECIOUS scales (r = 0.91 to 0.98) and demonstrated satisfactory internal consistency (α = 0.77 to 0.91) and test-retest reliability (ICCs > 0.70).

Conclusions

PRECIOUS-SF demonstrated internal consistency, convergent validity, test-retest reliability, and concurrent validity with PRECIOUS. PRECIOUS-SF offers a practical tool for routine quality of care assessment in pediatric serious illnesses for promoting timely service evaluation and quality improvement.
Beyond compliance: exploring the synergy of Islamic Fintech and CSR in fostering inclusive financial adoption
Authors: Alsmadi Ayman Abdalmajeed
Published: January 2025

Purpose

This research examines the relationship between Islamic Fintech and corporate social responsibility (CSR) in the pursuit of extending financial use to all layers of society. It aims at understanding key influencers such as Sharia compliance, perceived financial benefits, ease of technology uses and Islamic social responsibility (ISR) in the adoption of Islamic Fintech services. The study further investigates how culture may act as a moderator to the relationship between ISR and the adoption of Islamic Fintech services.

Research methodology

Data were collected from 263 respondents in Jordan using a structured questionnaire. The data were analyzed using Smart PLS software to test the proposed hypotheses and evaluate the research model’s reliability and validity.

Results and findings

The results reveal that Sharia compliance, perceived financial benefits, technological ease of use, and ISR significantly influence the adoption of Islamic Fintech services. The study also finds that cultural resonance plays a crucial moderating role, enhancing the impact of ISR on the adoption of these services.

Originality and empirical implications

This paper adds value to the existing literature by attempting a comprehensive analysis assessment of the reasons behind the adoption of Islamic Fintech. It highlights the necessity of connecting the modern-day financial systems and the ethical tenets practiced in societies to facilitate the nonconventional market penetration strategies. Such findings also provide useful articulations for Islamic Fintech providers who intend to respond to the changing dynamics within the rolling out of technology in a religious sustainable financing.
Improvement of Seismic Noise Cross-correlation Function by Phase-velocity Probability Density Selection
Authors: Sun Ruizhe , Li Jing , Liu Tieyu , Yan Yingwei , Liu Hui
Published: January 2025

TThe noise cross-correlation function (NCF) derived from continuous seismic records approximates the Green's Function (GF) of the far-field surface wave, which is crucial for S-wave velocity tomography. A critical step is stacking short-term NCFs over extended periods to improve the signal-to-noise ratio (S/N) and enhance the imaging quality of seismic data. However, incoherent noise significantly affects the accuracy of NCF calculations. Moreover, strong directional sources in the wavefield pose a challenge to conventional linear or phase-weighted stacking (PWS), often leading to overestimates of surface-wave phase velocity due to unresolved azimuthal effects. Selecting stationary phase zone (SPZ) data and correcting surface wave propagation paths based on source orientation requires a 2D array setup, which imposes stringent layout constraints. To address these challenges, we propose a novel data selection workflow for a 1D linear array based on the probability density distribution of surface-wave phase velocity. Firstly, we divide the noise data into different frequency bands and calculate the probability density curve of the phase velocity distribution for each frequency band. Then, based on the differences in phase velocities between SPZ data, directional source data, and incoherent noise, we select the probability density segments of SPZ data in each frequency band for stacking, effectively reducing the impact of incoherent noise and strong directional sources. The typical synthetic data and distributed acoustic sensing (DAS) field data examples demonstrate that the proposed workflow significantly improves the S/N in NCF and increases the useful bandwidth of the surface- waves dispersion curve, which furnishes reliable dispersion curve and waveform data, thereby facilitating subsequent S-wave velocity tomography.
On “Making Sure No One Ever Travels Too Far”: The Climate Novel and Our Limited Imagination
Authors: Nilges Mathias
Published: January 2025

Novelists whose work grapples with the climate crisis and the urgent need for structural transition return time and again to two questions: Why is it so hard for people to see what's happening? Why do we not seem to be able to imagine the transition to new environmental, social, or political systems? Authors of climate fiction show that environmental futures depend on our ability to renegotiate the limit between the “realistic” and the inconceivable, the boundary that strategically constrains our imagination and that limits social and environmental progress. How, authors ask, thereby responding to debates about the purported crisis of political and social futurity, should the novel respond to the sense that contemporary culture appears to be increasingly unable to generate convincing, hopeful visions of environmental and energy futures beyond capitalism? The contemporary novel engages with the problem of the limited imagination not as a way to dream up naive futures but rather to pinpoint the origins and causes of imaginative impossibility and obstacles to systemic transition. And by making legible the lack that is bound up with the limited imagination, the novel also asks how art itself functions as a specific form of critical and political thought.
The Death Cry of a Hen: Elizabeth Costello at Humanism's Impasse
Authors: Guha-Majumdar Jishnu
Published: January 2025

This article develops the ethico-political figure of the “cry” as a way of attending to the suffering of those on the underside of humanism. The author begins from the diagnosis that humanism—a worldview centered on the irreducible dignity of the human being by virtue of their humanity—is at an “impasse,” in the way that Lauren Berlant uses the term. That is, the fantasies of a fully realized liberal humanism seem increasingly costly, while alternatives feel out of reach. Turning to J. M. Coetzee's novel Elizabeth Costello, specifically its chapters on the lives of animals, the author revamps work on the ethics of vulnerability to offer one way of negotiating this impasse without necessarily resolving it. Beginning from the moment when the novel's protagonist describes the effects of a hen's cry as she is put to death, the article posits the cry as the irruption of vulnerability that is proper neither to animality or humanity. Irreducible to voice or speech, the cry is a quivering movement that threatens the coherency of vocal capacity. Attention to it creates the possibility of becoming undone, of reorienting maps of suffering, and of entering into new relationships with those on the underside of hegemonic humanism.