bluuebunny/crossref_metadata_2025 huggingface dataset:
How online healthcare team evolve into organization: A social network analysis
Authors: Ding Xiaoyan , Zhang Xin , Wang Wen Hao , You Xiang
Published: October 2024

Objective

The rapid development of online healthcare has greatly promoted the transformation of healthcare service. The effectiveness of online healthcare is enhanced by the team that supports the doctor–patient connection. However, extant researches lack the comprehensive analysis of social networks within online healthcare team. In this study, we aim to clarify the characteristics and models of online healthcare team.

Method

This study focuses on the online healthcare context and collects data from online healthcare team. Using social network analysis, the social networks of online healthcare members are also developed as part of the research.

Result

This study uncovers the different modes of online healthcare teams from individual, team and organizational levels. These results shed light on the characteristics of an online healthcare team and show that such teams are capable of restructuring social networks. In addition, collaboration between teams allows for the development of multilevel relationships and the potential for the online healthcare team to evolve into a large-scale online healthcare organization.

Conclusion

Through social network analysis, this study offers a fresh viewpoint on online healthcare and its implications for management, team construction, and organizational restruction. By examining the characteristics and models of online healthcare team, this research offers valuable insights for improving the overall effectiveness of online healthcare.
Peasant Agency in a Changing Agrarian Situation in Central Zimbabwe: The Case of Mhondoro Ngezi
Authors: Mkodzongi Grasian
Published: October 2024

This article explores peasant agency during a changing agrarian situation in Zimbabwe. The article pays particular attention to the way landless peasants deployed ‘weapons of the weak’ such as illegal extension of plots beyond the boundaries marked by Ministry of lands officials, encroachment on common grazing lands, and faking membership of the Zimbabwe African National Union–Patriotic Front (ZANU-PF) to gain access to land. This demonstrates peasant agency and resistance which has so far received limited attention in the literature.
Thirty Years of Urban Bias: An Estimation of the Rising Disparities in Female Rural and Female Urban Unemployment and Income in Egypt
Authors: Helmy Heba E.
Published: October 2024

This article highlights the disparities between female urban and rural employment and income in Egypt over the last decades, mainly resulting from urban bias policies. Despite their inferior educational levels, females in rural Egypt manifested higher levels of employment than their counterparts in urban Egypt, a phenomenon that the article attributes to the standard definition of unemployment, which includes unpaid family members as part of the ‘employed’, besides other methodological issues. As such, statistics could misleadingly imply better female rural income compared to female urban income. By means of an innovative attempt to estimate female rural and urban incomes, this article provides some evidence that female rural per capita income accounts for only 0.43 of female urban per capita income, despite rising from 0.2 in 1981. The female rural/urban gap was mitigated when female national incomes rather than female per capita incomes were estimated, with female rural national income accounting for nearly 0.73 of female urban national income.
Book review: Hugo Chávez (2013), Mi Primera Vida: Conversaciones con Ignacio Ramonet [My First Life: Conversations with Ignacio Ramonet]
Authors: Schincariol Vitor E.
Published: October 2024

Hugo Chávez (2013), Mi Primera Vida: Conversaciones con Ignacio Ramonet [My First Life: Conversations with Ignacio Ramonet], Barcelona, Spain: Debate. ISBN 978-8499923772 (Hardback), pp. 728. Price €25.55.
Primary Ewing’s Sarcoma of the Sternum in an Adult Male: A Rare Case Report
Authors: Qupp Salem K. , Halayqa Iyad M. , Shawahna Eman J. , Bdair Amjad , Madaka Seham , Issa Majd , Jawabreh Ola , Awaysa Asala Mohammad , Al-Karaja Layth , Abosleem Abedalrahman
Published: October 2024

Ewing’s sarcoma, a rare primary bone malignancy primarily affecting adolescents and young adults, typically manifests in the pelvic bones and femur. Primary Ewing’s sarcoma of the sternum is exceptionally rare, constituting less than 1% of cases. We present a case of a 34-year-old man with a 2-month history of anterior chest wall pain initially attributed to muscular spasm. Subsequently, the patient developed a palpable mass and imaging demonstrated a mid-lower sternal lesion with cortical destruction and soft tissue involvement, confirmed as Ewing’s sarcoma on biopsy. In addition, a suspicious lesion was identified in the left distal tibia, which was histologically confirmed as a metastasis from the primary sternal sarcoma. Neoadjuvant chemotherapy preceded partial sternotomy with rib resection and reconstruction, achieving clear surgical margins. Postoperative evaluation showed shrinkage in the sternal lesion and near-resolution of the tibial metastasis. Subsequent chemotherapy cycles resulted in no evidence of the disease on the follow-up positron emission tomography scan. This case underscores the diagnostic challenges of primary sternal Ewing’s sarcoma and emphasizes the importance of early recognition and comprehensive evaluation in managing such rare presentations.
俄亚、白地东巴文化调查研究》 评介
Authors: 张 春凤
Published: October 2024

《俄亚、白地东巴文化调查研究》是一本新近出版的纳西学补缺之作，以俄亚和白地为研究对象，以语言文字文献研究为重点内容，涉及多个学科。该书通过持久田野调查搜集了丰富的材料，关注东巴群体，记录了俄亚和白地的语音，为两地东巴经进行了编目和翻译，对应用性文献进行了深入研究。
Dry eye disease in episodic and chronic migraine: A cross-sectional clinic-based study
Authors: Chowdhury Bithi , Kumar Pradeep , Sharma Hemant , Chowdhury Debashish
Published: October 2024

Background

Dry eye disease (DED) and migraine, two common disorders with public health concerns, may have a bidirectional relationship. Population-based studies have found that migraine patients have higher odds of DED and vice versa. We aimed to evaluate and compare the presence of DED symptoms and objective signs between migraine patients and non-migraine controls.

Methods

This was a case-control study. We prospectively enrolled 60 consecutive migraine patients (30 episodic and 30 chronic) presenting in the medicine outpatient department, aged 18–65 years, and 60 non-migraine healthy controls visiting the ophthalmology department for refractive errors between February 2019 and June 2021. Consecutive migraine patients and non-migraine healthy controls were assessed in the ophthalmology department at Hindu Rao Hospital, Delhi by the Ocular Disease Surface Index (OSDI) questionnaire for DED symptoms and objectively by measuring tear break-up time (TBUT), Schirmer test (ST), and Fluorescein staining (FS). DED severity was assessed by the Odessey algorithm.

Results

The mean OSDI score was significantly greater in migraineurs than in controls (31.2 ± 19.8 vs 22.7 ± 15.6; p = 0.010). 45% of migraineurs had DED compared to 18.3% in controls (p = 0.002), whereas 23.3% had severe DED compared to one (1.7%) in the control group (p < 0.001). Migraineurs, compared to controls, had significantly lower mean TBUT (10.1 ± 6.5 s versus 13.4 ± 5.8 s; p = 0.004), higher FS grade (1.57 ± 1.4 versus 0.92 ± 1.2; p = 0.008) and lower ST scores (11.5 ± 5.8 mm versus 14.2 ± 6.2 mm; p = 0.014). Migraineurs with DED, compared with those without DED, had longer migraine disease duration, higher frequency, pain severity, and disability. Compared to episodic migraine, chronic migraine patients had significantly lower TBUT (11.9 ± 5.9 vs 8.3 ± 6.7; p = 0.30) and higher OSDI scores (25.7 ± 20.1 vs 36.8 ± 18.2).

Conclusions

This study showed that migraine patients had an increased presence of DED and severe DED compared to controls. Further, increased migraine severity and chronicity were associated with increased subjective symptoms and objective signs of DED. Migraine patients with DED were more disabled.CM patients had more DED symptoms and signs.
Dysphagia After Cervical Spinal Surgery: An Assessment of Incidence and Predisposing Factors
Authors: Eriksson Sven E. , Ohde Jane , Zheng Ping , Sarici Inanc S. , Jobe Blair A. , Ayazi Shahin
Published: October 2024

Background:

Dysphagia is common following cervical spinal surgery (CSS) yet reported incidence and risk factors are highly heterogeneous. This case-control study aimed to determine the incidence of dysphagia after CSS and identify its predisposing factors.

Methods:

Records of 1199 patients who underwent CSS over a 2-year period at our center were reviewed. Patients with postoperative dysphagia and an equal number of randomly selected patients without dysphagia were included for analysis. Demographic, clinical, intraoperative, and perioperative factors were compared using univariate followed by multivariable logistic regression analysis.

Results:

The study population consisted of 94 (7.8%) patients with dysphagia and 94 controls. Patients with postoperative dysphagia were older [mean (SD) 60.7(12) vs 54.7(12), P = .002] and more likely to have preoperative dysphagia (16% vs 0%, P < .001). No other demographic or clinical factors were significant. Mid-level (C3-4, C4-5) (66% vs 48%, P = .018) and multilevel surgeries (67% vs 50%, P = .026) were associated with dysphagia. No other intraoperative factors were significant. The presence of any (abscess, dehiscence, hematoma, CSF leak, prevertebral edema, esophageal, or vocal cord injury) perioperative complication (20% vs 3.2%, P < .001) was associated with dysphagia, with dehiscence (6.5% vs 0%, P = .029) and hematoma (6.5% vs 0%, P = .029) showing the strongest association. Multivariable analysis identified age ≥70 [OR (95% CI): 2.8 (1-7), P = .031] and any perioperative complication [OR (95% CI): 6.7 (2-25), P = .004] as independent predictors of dysphagia.

Conclusion:

The incidence of dysphagia after cervical spine surgery is 7.8%. The risk of postoperative dysphagia is 6.7-times higher in those with perioperative complications and 2.8-times higher in patients over 70.
Spring-Assisted Cranioplasty in Unicoronal Synostosis: Analysis of Outcomes
Authors: Frommer Sarah Anne , Combs Patrick Duffy , Tyler-Kabara Elizabeth Christine , Kelley Patrick Kevin
Published: October 2024

Background:

Spring-assisted cranioplasty and successful long-term outcomes for sagittal synostosis has been well described in recent literature. However, there is a paucity of data regarding the application of springs to unicoronal synostosis. Unicoronal synostosis (UCS) presents unique challenges in its causation of skull base scoliosis and orbital asymmetry. Many surgeons feel that the fronto-orbital advancement and vault remodeling is the most effective and reliable strategy to counteract these changes. Here we present our experience and outcomes with spring cranioplasty for unicoronal synostosis.

Materials and methods:

A retrospective review of non-syndromic unicoronal synostosis patients undergoing spring-assisted cranioplasty was performed. Preoperative and postoperative intracranial volume (ICV), orbital volume (OV), orbital height (OH), orbital width (OW), midface twist (MFT), and skull-base twist (SBT) were measured from DICOM CT data. Analysis was performed with Materialize software (Leuven, Belgium). Paired t-tests were performed using Excel.

Results:

Ten patients (5 females, 5 males) had springs placed at 100.1 days (avg). Average ICV: preop: 608.2 ± 101.4 cc, postop: 995.2 ± 166.1 cc. Differences in orbital volume and height in the preop affected orbit versus non-affected orbit was significant ( P = .01, P ≤ .001 respectively) whereas no significant difference between the two sides postoperatively was observed ( P = .19, P = .58 respectively). Average preop MFT was 81.1 ± 2° and postop was 87.6 ± 2.6° and preop SBT was 171.9 ± 2.7° and postop was 177.6 ± 2.6°; both showing significant improvement after spring cranioplasty (both P ≤ .001).

Conclusion:

Our experience and early outcomes with spring cranioplasty for UCS demonstrates that when used in younger patients (<5 months) cranial springs can be a safe and effective strategy to minimize skull base scoliosis, facial scoliosis, and orbital asymmetry, as well as increase intracranial volume. Although long-term data needs to be assessed, we are optimistic that early correction of cranial base scoliosis will translate to stable results as patients reach dentoskeletal maturity.
Estimation of photovoltaic production using Spline fitting and TSCI
Authors: López-Meraz Raúl Alberto , Méndez-Ramírez Ce Tochtli , Jamed-Boza Luis Omar
Published: October 2024

This study presents an alternative methodology for analyzing the difference in daily solar energy generation between two grid-connected photovoltaic arrays (PVAs) that are identical in capacity, technical characteristics, and have the same energy production measurement interval but are in two different municipalities of Mexico City (CDMX). Unlike conventional approaches, which often rely on environmental variables, this work proposes combining the cubic smoothing Spline technique with the separation of trend, seasonality, and cyclicality (TSCI) effects. The first technique reduces random variations in measurement, while the second separates the effects commonly found in time series data. The results obtained are useful for installers of this technology, as they allow them to determine in which borough a greater photovoltaic capacity is needed.
Commentary on Juval Portugali's ‘Bohm's theory of orders as a basis for a unified urban theory’
Authors: Morçöl Göktuğ
Published: October 2024

Portugali's proposal to unify urban theory based on Bohm's theory of quantum phenomena is discussed. The propositions of complexity theory and phenomenology are compared, and it is argued that their ontologies and epistemologies cannot be easily reconciled. It is argued that Bohm's theory is compatible with complexity theory but does not help bridge the differences between complexity theory and phenomenology. A grand unification of urban theory, the way Portugali envisions it, does not seem to be possible.
On conceptual hegemony and blanqueamiento vis-a-vis Latin urbanism in London
Authors: Román-Velázquez Patria
Published: October 2024

The commentary focuses on two arguments addressed in the article which resonates with my research about Latin America's urban margins and Latin urbanisms in London. It will first address gentrification's conceptual hegemony and its adoption in other regions of the world where neither its translation nor conceptual understanding suffice or allow for broader nuances of the processes embedded in urban change. It will then discuss the use of blanqueamiento as a concept vis-a-vis Latin urbanism in London to argue for the need of dialogical regional interconnections.
Modes of existence, capitalism, and lived socio-ecological struggles: Whither actor-network theory in a world in crisis?
Authors: Nimmo Richie
Published: October 2024

In response to the forum article ‘What Next for Actor-Network Theory?’, this piece takes up the suggestion that a fruitful way forward for actor-network theory (ANT) would be to engage with ideas ‘originating from elsewhere’, such as from other theoretical traditions. Examining this, I suggest that the version of ANT brought into such dialogue matters, and that – contrary to the suggestion of the forum article – Latour's late ‘modes of existence’ project is not the most conducive for this purpose. I then assess the prospects for a productive cross-fertilisation between a less meta-ontological articulation of ANT and other theoretical repertoires, identifying an obstacle to this in the tendency of ANT to use other traditions of social thought largely as a foil against which to define itself, which mitigates against proper engagement with the strengths of those traditions. Taking a lead from the examples discussed in the forum article, I flesh this out by highlighting some of the shortcomings of ANT, relative to political ecology for instance, as a way of understanding socio-ecological relations and conflicts, in part because of its habitual disdain for certain sorts of ‘grand abstractions’, in particular, ‘capitalism’. I argue conversely that such abstractions not only speak to the lived realities of historically embedded structural violence and dispossession at the heart of socio-ecological struggles, but are crucial for situating people's lives in the context of wider relations and processes, something one might well deem a key purpose of sociology.
Effects of source, path, and site conditions on damping modification factor for the horizontal response spectrum using offshore ground motions in the Japan Trench area
Authors: Liu Mingji , Hu Jinjun , Tan Jingyang
Published: October 2024

In the seismic design, analysis, and risk assessment for engineering structures, the intensity of ground shaking was typically predicted using ground motion prediction models with a 5% damping ratio. However, given the broader range of damping ratios observed in marine structures, it was necessary to scale spectral ordinates using damping modification factor (DMF). This statistical study was conducted based on 6676 records of offshore ground motion, obtained from S-net located in the Japan Trench. Conducting an examination into source parameters (magnitude, focal depth, earthquake types), source distance, and site parameters (sediment thickness, water depth, burial conditions), the study explored the effects of these parameters on DMFs, assessed their influence rankings through correlation analysis, and scrutinized a model form incorporating these parameters via residual analysis of the default model proposed in the study. It was shown that significant differences in DMFs among buried conditions of ground motion recordings, with magnitude being the most influential factor, followed by source distance and water depth, while focal depth and sediment thickness have the least impact on DMF. Furthermore, this study proposed a default model that takes into account buried conditions, along with a proposed median model that incorporates the default model, source and path effect function, as well as their standard deviation models. It was observed that the reduction in uncertainty of the proposed median model is primarily attributed to the decrease in between-event uncertainty, resulting in an average decrease of 20% in total standard deviation.
How I diagnose and treat cardiorespiratory complications of transfusion
Authors: Vlaar Alexander P , Zwaginga Jaap Jan , Wiersum-Osselton Johanna C
Published: October 2024

Cardiorespiratory complications after blood transfusion are the leading cause of transfusion related morbidity and mortality world-wide. Transfusion-related acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) form the top two most frequently reported cardiorespiratory complications, both with clear pathophysiology-based treatment algorithms. In the past decades translational research has increased understanding of mechanisms in place including patient and transfusion risk factors. This has led to updated international definitions, biomarker-based diagnostics, intervention and risk mitigation. Preventive measures have led to a significant reduction in TRALI and TACO prevention is increasingly highlighted within hemovigilance. In this paper clinical case scenarios illustrate the challenges of diagnosing, treating and finally classifying cardiorespiratory complications of transfusion. A background on current definitions, diagnostics and pathophysiological mechanisms will be given; as well as how to deal with cases where TRALI/ TACO mechanisms are both present and need for combination therapies. Hemovigilance systems world-wide are essential to provide insight into the incidence of transfusion complications. Furthermore, these systems provide a basis to discover new patient and transfusion risk factors and to better balance the down- and upside of a transfusion for a patient. Finally, we discuss future challenges and research priorities in the field of cardiorespiratory transfusion complications.
Follicular lymphoma comprises germinal center–like and memory-like molecular subtypes with prognostic significance
Authors: Laurent Camille , Trisal Preeti , Tesson Bruno , Seth Sahil , Beyou Alicia , Roulland Sandrine , Lesne Bastien , Van Acker Nathalie , Cerapio Juan-Pablo , Chartier Loïc , Guille Arnaud , Stokes Matthew E. , Huang C. Chris , Huet Sarah , Gandhi Anita K. , Morschhauser Franck , Xerri Luc
Published: October 2024

A robust prognostic and biological classification for newly diagnosed follicular lymphoma (FL) using molecular profiling remains challenging. FL tumors from patients treated in the RELEVANCE trial with rituximab-chemotherapy (R-chemo) or rituximab-lenalidomide (R2) were analyzed using RNA sequencing, DNA sequencing, immunohistochemistry (IHC), and/or fluorescence in situ hybridization. Unsupervised gene clustering identified 2 gene expression signatures (GSs) enriched in normal memory (MEM) B cells and germinal center (GC) B-cell signals, respectively. These 2 GSs were combined into a 20-gene predictor (FL20) to classify patients into MEM-like (n = 160) or GC-like (n = 164) subtypes, which also displayed different mutational profiles. In the R-chemo arm, patients with MEM-like FL had significantly shorter progression-free survival (PFS) than patients with GC-like FL (hazard ratio [HR], 2.13; P = .0023). In the R2 arm, both subtypes had comparable PFS, demonstrating that R2 has a benefit over R-chemo for patients with MEM-like FL (HR, 0.54; P = .011). The prognostic value of FL20 was validated in an independent FL cohort with R-chemo treatment (GSE119214 [n = 137]). An IHC algorithm (FLcm) that used FOXP1, LMO2, CD22, and MUM1 antibodies was developed with significant prognostic correlation with FL20. These data indicate that FL tumors can be classified into MEM-like and GC-like subtypes that are biologically distinct and clinically different in their risk profile. The FLcm assay can be used in routine clinical practice to identify patients with MEM-like FL who might benefit from therapies other than R-chemo, such as the R2 combination. This trial was registered at www.clinicaltrials.gov as #NCT01476787 and #NCT01650701.
Cost-effectiveness of iptacopan for paroxysmal nocturnal hemoglobinuria
Authors: Ito Satoko , Chetlapalli Karthik , Wang Daniel , Potnis Kunal C. , Richmond Rhys , Krumholz Harlan M. , Lee Alfred I. , Cuker Adam , Goshua George
Published: October 2024

Iptacopan, a novel oral factor B inhibitor, recently obtained US Food and Drug Administration approval for treating paroxysmal nocturnal hemoglobinuria, a rare blood disorder characterized by persistent complement-mediated hemolytic anemia. The standard-of-care (SOC) has traditionally relied on complement C5 inhibitors eculizumab and ravulizumab, which are limited by persistent anemia from extravascular hemolysis and requirement for intravenous infusion. Recent publication of phase 3 studies in this arena reinforces iptacopan as an effective anticomplement monotherapy compared with SOC. Given ongoing price negotiations and limited literature showing its cost-ineffectiveness in the anti-C5–treated population, we conducted a comprehensive cost-effectiveness analysis of iptacopan monotherapy in anti-C5–treated patients from the societal perspective, as compared with C5 inhibition. The primary outcomes were the incremental net monetary benefit across a lifetime horizon and the cost-effective maximum monthly threshold price of iptacopan monotherapy compared with the SOC. The secondary outcome was time saved for patients and nurses with the use of oral iptacopan therapy. Iptacopan monotherapy and SOC accrued 12.6 and 10.8 quality-adjusted life-years at costs of $9.52 million and $13.5 million, respectively. Iptacopan monotherapy remained cost saving across extensive sensitivity and all scenario analyses, including alternative parameterization for anemia resolution and aggregated individual-level utilities and transition probability matrix. Across all probabilistic sensitivity analyses, iptacopan monotherapy was favored over SOC in 100% of 10 000 Monte Carlo iterations. Cost-saving thresholds for iptacopan vs anti-C5 are ∼1.1, 1.4, and 1.4 in Brazil, Japan, and the United States, respectively. Iptacopan monotherapy can improve quality-adjusted life expectancy for patients while saving health care costs across jurisdictions.
Social determinants of health affect disease severity among preschool children with sickle cell disease
Authors: Khan Hamda , Kang Guolian , Porter Jerlym S. , Ding Juan , Wang Winfred C. , Estepp Jeremie H. , Gurney James G. , Davis Robert , Hankins Jane S. , Hodges Jason R.
Published: October 2024

Individuals with sickle cell disease (SCD) face the burden of managing a lifelong chronic illness, increasing vulnerability to social determinants of health (SDoH). However, how SDoH contributes to health disparities is understudied. We hypothesized that preschool children with SCD living in poor neighborhoods with higher socio-economic distress would experience increased acute care utilization (ACU; described as emergency department visits plus hospitalizations) despite disease-modifying therapy. Participants' home addresses (aged 0-6 years) were mapped using census tract environmental data from the US Department of Agriculture Food Access Research Atlas. In multivariable analyses controlled for sickle genotype and disease-modifying therapies (hydroxyurea and chronic transfusion), SDoH indicators, that is, limited access to food, lack of vehicle, low income, and inadequate education, were associated with higher ACU. Living in households with children >1 mile from a supermarket was associated with more hospitalizations (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.13-1.85) and ACU (OR, 1.37; 95% CI, 1.06-1.80) among children with SCD (aged <6 years). In households with at least 1 bachelor's degree, children with SCD experienced less ACU (OR, 0.67; 95% CI, 0.50-0.93) and hospitalizations (OR, 0.67; 95% CI, 0.49-0.92). Preschool children with SCD with limited access to food and transportation are at a higher risk of acute complications despite receiving free evidence-based therapy and social support. The family education level may have a protective effect. Although SDoH in crowded households and health care maintenance visits were not a focus of this study, future research should consider these factors. Understanding the SCD and SDoH association is crucial for directing resources to improve affected children's health.
Unbiased high-throughput screening of drug-repurposing libraries identifies small-molecule inhibitors of clot retraction
Authors: Buitrago Lorena , Menezes Miriam-Rose , Larson Chloe , Li Jihong , Kartika Thomas , Banerjee Priyam , Glickman Fraser , Coller Barry
Published: October 2024

Platelet clot retraction, the ultimate phase of platelet thrombus formation, is critical for clot stabilization. It requires functional αIIbβ3 receptors, fibrin, and the integrated actions of the actin-myosin contractile and cytoskeletal systems. Disturbances in clot retraction have been associated with both bleeding and thrombosis. We recently demonstrated that platelets treated with the αIIbβ3 antagonist peptide Arg-Gly-Asp-Trp, which eliminates fibrinogen-mediated platelet aggregation, are still able to retract clots. We have exploited this observation to develop an unbiased, functional high-throughput assay to identify small-molecule inhibitors of fibrin-mediated clot retraction adapted for a 384-well plate format. We tested 9710 compounds from drug-repurposing libraries (DRLs). These libraries contain compounds that are either US Food and Drug Administration approved or have undergone preclinical/clinical development. We identified 27 compounds from the Library of Pharmacologically Active Compounds library as inhibitors of clot retraction, of which 14 are known inhibitors of platelet function. From the DRLs, we identified 135 compounds (1.6% hit rate). After extensive curation, these compounds were categorized based on the activity of their reported target. Multiple kinase and phosphodiesterase inhibitors with known antiplatelet effects were identified, along with multiple deubiquitination and receptor inhibitors, as well as compounds that have not previously been reported to have antiplatelet activity. Studies of 1 of the deubiquitination inhibitors (degrasyn) suggest that its effects are downstream of thrombin-induced platelet-fibrinogen interactions and thus may permit the separation of platelet thrombin-induced aggregation-mediated events from clot retraction. Additional studies of the identified compounds may lead to novel mechanisms of inhibiting thrombosis.
Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition
Authors: Williams Matthew J. , Wang Xiaonan , Bastos Hugo P. , Grondys-Kotarba Gabriela , Wu Qin , Jin Shucheng , Johnson Carys , Mende Nicole , Calderbank Emily , Wantoch Michelle , Park Hyun Jung , Mantica Giovanna , Hannah Rebecca , Wilson Nicola K. , Pask Dean C. , Hamilton Tina L. , Kinston Sarah J. , Asby Ryan , Sneade Rachel , Baxter E. Joanna , Campbell Peter , Vassiliou George S. , Laurenti Elisa , Li Juan , Göttgens Berthold , Green Anthony R.
Published: October 2024

Adult hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells, a process regulated by extracellular cues, including cytokines. Many cytokines signal through the conserved Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in which tyrosine-phosphorylated STATs (pSTATs) function as transcription factors. STAT5 is a pivotal downstream mediator of several cytokines known to regulate hematopoiesis, but its function in the HSC compartment remains poorly understood. In this study, we show that STAT5-deficient HSCs exhibit an unusual phenotype, including reduced multilineage repopulation and self-renewal, combined with reduced exit from quiescence and increased differentiation. This was driven not only by the loss of canonical pSTAT5 signaling, but also by the loss of distinct transcriptional functions mediated by STAT5 that lack canonical tyrosine phosphorylation (uSTAT5). Consistent with this concept, expression of an unphosphorylatable STAT5 mutant constrained wild-type HSC differentiation, promoted their maintenance, and upregulated transcriptional programs associated with quiescence and stemness. The JAK1/2 inhibitor, ruxolitinib, which increased the uSTAT5:pSTAT5 ratio, had similar effects on murine HSC function; it constrained HSC differentiation and proliferation, promoted HSC maintenance, and upregulated transcriptional programs associated with stemness. Ruxolitinib also enhanced serial replating of normal human hematopoietic stem and progenitor cells (HSPCs), calreticulin-mutant murine HSCs, and HSPCs obtained from patients with myelofibrosis. Our results therefore reveal a previously unrecognized interplay between pSTAT5 and uSTAT5 in the control of HSC function and highlight JAK inhibition as a potential strategy for enhancing HSC function during ex vivo culture. Increased levels of uSTAT5 may also contribute to the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.
Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease
Authors: John Tami D. , Walters Mark C. , Rangarajan Hemalatha G. , Rahim Mahvish Q. , McKinney Christopher , Bollard Catherine M. , Abusin Ghada , Eapen Mary , Kassim Adetola A. , DeBaun Michael R.
Published: October 2024

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 leadership and the data safety monitoring board (DSMB) established incremental entry criteria for children aged 5 to 14.99 years with sickle cell disease (SCD) enrolling in a phase 2 trial of HLA-haploidentical hematopoietic stem cell transplantation. First, the enrollment was limited to overt stroke in the first 10 participants (stage 4). Subsequently, the DSMB reviewed the interim results and expanded the eligibility to include children with silent cerebral infarcts or abnormal transcranial Doppler velocities with magnetic resonance angiography–defined cerebral vasculopathy (stage 3). A third cohort was enrolled after the DSMB reviewed the clinical outcomes in these cumulative initial enrollments (n = 18) and additions were made to the entry criteria that included nonneurologic morbidities (stage 2). Added eligibility criteria included the following: (1) life-threatening acute chest syndrome requiring exchange transfusion; (2) right heart catheterization confirmed pulmonary hypertension; (3) persistent systemic hypertension despite maximum medical therapy; (4) acute pain despite maximum medical therapy in the absence of psychosocial factors and unmanaged asthma after adjudication; and (5) 2 major priapism episodes in 12 months or 3 in 24 months. Children with SCD who did not meet the criteria for stages 4, 3, and 2 were not eligible. To our knowledge, for the first time, we introduce a staged strategy for eligibility in a curative therapy trial for children with SCD concordant with 45 Code of Federal Regulations § 46.405(b). The research governance–mandated eligibility strategy used within the BMT CTN 1507 phase 2 study may apply to future pediatric SCD curative therapy trials. This trial was registered at www.ClinicalTrials.gov as #NCT032635590.
Sustained remission at long term follow-up in adolescents and young adults with chronic primary immune thrombocytopenia
Authors: Schifferli Alexandra , Le Gavrian Gautier , Aladjidi Nathalie , Moulis Guillaume , Godeau Bertrand , Leblanc Thierry , Héritier Sébastien , Fernandes Helder , Kühne Thomas
Published: October 2024

Adolescents and young adults (AYAs) with immune thrombocytopenia (ITP) exhibit distinct clinical features and needs, defying categorization as either adults or children. Previous findings revealed a 50% risk of chronic disease at 12 months, yet the long-term course remains unclear. This study aimed to delineate the clinical and laboratory characteristics of AYAs with chronic primary ITP. Data from patients aged 12 to 25 years with chronic disease at 1 year were extracted from 3 registries (Pediatric and Adult Registry on Chronic ITP, CEREVANCE, and Cytopénies Auto-immunes Registre Midi-Pyrénéen), covering the period from 2004 to 2021. Sustained complete remission off treatment (SCROT) occurring beyond 12 months was defined as platelet count of >100 × 109/L without treatment for at least 12 months, independently of the previous treatment strategy. A total of 427 AYAs (64% female) with chronic primary ITP were included. Clinical information was available for ∼100% of patients at initial diagnosis and at 6- and 12-month follow-ups (FUs); and for 88%, 77%, and 59% at 24, 36, and 48 months, respectively. Over time, clinical features improved gradually, with fewer patients requiring treatment. Throughout the FU period, second-line drug use increased steadily among treated patients, without affecting the need for corticosteroids and IV immunoglobulins. The proportion of new patients achieving SCROT at 24-, 36-, and 48-month FU was 10% (38/375), 9.5% (31/327), and 12% (30/250), respectively, including 23 who underwent splenectomy. AYAs achieving SCROT between 12 and 36 months displayed higher platelet counts in the first year (excluding the initial period) and received fewer IV immunoglobulin treatments beyond 12 months compared with those with ongoing disease.
Biologically synthesized nanoparticles: barley-mediated silver and gold nanoparticles and caged gold nanoplatform for advanced drug delivery system engineering in medicine
Authors: Talaat Muhammad
Published: October 2024

The integration of green synthesis methods and advanced nanostructure designs holds significant promise for the development of innovative nanomaterials with diverse biomedical applications. This commentary delves into the use of barley grains for the eco-friendly synthesis of silver and gold nanoparticles, highlighting their potential as biocompatible agents with potent antibacterial properties. The barley-mediated synthesis approach not only offers a sustainable and cost-effective method for producing these nanoparticles but also underscores their remarkable efficacy against pathogenic bacteria. The barley-mediated approach not only offers a sustainable and cost-effective method for producing biocompatible nanoparticles but also demonstrates remarkable antibacterial efficacy against pathogenic bacteria. By critically evaluating the strengths and potential gaps in this synthesis approach, this commentary emphasizes the importance of integrating green synthesis techniques with advanced nanoparticle applications. Future research directions should aim at optimizing synthesis processes, ensuring enhanced stability and biocompatibility, and exploring the full potential of biologically synthesized nanoparticles in medical treatments and environmental sustainability. This focus on sustainable synthesis and application could pave the way for the next generation of nanomaterials, offering significant advancements in both healthcare and ecological preservation. By examining the strengths, gaps, and potential synergies between these two approaches, this commentary underscores the importance of sustainable synthesis techniques and the development of multifunctional nanoparticles. This integrated approach could lead to the creation of next-generation nanomaterials, offering significant advancements in medical treatments and environmental sustainability.
Characterization of infectious bacterial keratitis in Östergötland County, Sweden: a 10-year retrospective study
Authors: Roth Jenny , Toprak Baris , Somajo Sofia , Macedo Antonio Filipe , Lagali Neil
Published: October 2024

Background

The aim of this study was to characterize bacterial species, aetiology and antibiotic susceptibility connected to bacterial keratitis infections in Östergötland, Sweden.

Methods

Retrospective cross-sectional study based on electronic health records for the period 2010–2019. Records of patients diagnosed with infectious keratitis were screened for microbiology confirmed infectious bacterial keratitis. Bacterial species and their susceptibility to antibiotics were determined from microbiology test results.

Results

One-hundred and ninety patients with lab culture-confirmed infectious bacterial keratitis were included in the analysis. The most frequently found bacterial species were coagulase-negative staphylococci (39%), Staphylococcus aureus (17%) and Cutibacterium acnes (10%). Pseudomonas spp. was the most frequently found Gram-negative bacterial species (7%). Contact lens wear and severely ill/blind eye were the top two aetiologies associated with bacterial keratitis, 22% of the patients with bacterial keratitis were also diagnosed with glaucoma. Most isolates, 157 out of 173, were susceptible to fluoroquinolones, and 145 out of 155 isolates were susceptible to chloramphenicol.

Conclusion

Our results revealed a positive rate of bacterial keratitis of 59% for the samples sent to the laboratory. There was a high susceptibility of the bacterial species to the recommended antibiotics. Our results indicate that it is likely that patients are receiving the correct treatment. Future studies are necessary to monitor changes in antibiotic susceptibility.
Are there conserved biosynthetic genes in lichens? Genome-wide assessment of terpene biosynthetic genes suggests ubiquitous distribution of the squalene synthase cluster
Authors: Singh Garima , Pasinato Anna , Yriarte Alejandra López-Chicheri , Pizarro David , Divakar Pradeep K. , Schmitt Imke , Dal Grande Francesco
Published: October 2024

Lichen-forming fungi (LFF) are prolific producers of functionally and structurally diverse secondary metabolites, most of which are taxonomically exclusive and play lineage-specific roles. To date, widely distributed, evolutionarily conserved biosynthetic pathways in LFF are not known. However, this idea stems from polyketide derivatives, since most biochemical research on lichens has concentrated on polyketide synthases (PKSs). Here, we present the first systematic identification and comparison of terpene biosynthetic genes of LFF using all the available Lecanoromycete reference genomes and 22 de novo sequenced ones (111 in total, representing 60 genera and 23 families). We implemented genome mining and gene networking approaches to identify and group the biosynthetic gene clusters (BGCs) into networks of similar BGCs. Our large-scale analysis led to the identification of 724 terpene BGCs with varying degrees of pairwise similarity. Most BGCs in the dataset were unique with no similarity to a previously known fungal or bacterial BGC or among each other. Remarkably, we found two BGCs that were widely distributed in LFF. Interestingly, both conserved BGCs contain the same core gene, i.e., putatively a squalene/phytoene synthase (SQS), involved in sterol biosynthesis. This indicates that early gene duplications, followed by gene losses/gains and gene rearrangement are the major evolutionary factors shaping the composition of these widely distributed SQS BGCs across LFF. We provide an in-depth overview of these BGCs, including the transmembrane, conserved, variable and LFF-specific regions. Our study revealed that lichenized fungi do have a highly conserved BGC, providing the first evidence that a biosynthetic gene may constitute essential genes in lichens.
Participants’ baseline characteristics and feedback of the nature-based social intervention “friends in nature” among lonely older adults in assisted living facilities in finland: a randomised controlled trial of the RECETAS EU-project
Authors: Pitkala Kaisu H. , Rautiainen Laura , Aalto Ulla L. , Kautiainen Hannu , Kolster Annika , Laakkonen Marja-Liisa , Partonen Timo , Roitto Hanna-Maria , Strandberg Timo E. , Opacin Nerkez , Puntscher Sibylle , Siebert Uwe , Coll-Planas Laura , Sachs Ashby L. , Litt Jill S. , Jansson Anu H. ,   For the RECETAS project, David Acurio , Alzbeta Bártová , Lucie Cattaneo , Iva Holmerova , Gabriela Garcia
Published: October 2024

Background

Loneliness is common among older adults in institutional settings. It leads to adverse effects on health and wellbeing, for which nature contact with peers in turn may have positive impact. However, the effects of nature engagement among older adults have not been studied in randomised controlled trials (RCT). The “Friends in Nature” (FIN) group intervention RCT for lonely older adults in Helsinki assisted living facilities (ALFs) aims to explore the effects of peer-related nature experiences on loneliness and health-related quality of life (HRQoL). In this study we aim describe the participants’ baseline characteristics of the RCT, feasibility of FIN intervention and intervention participants’ feedback on the FIN.

Methods

Lonely participants were recruited from 22 ALFs in Helsinki area, Finland, and randomised into two groups: 1) nature-based social intervention once a week for nine weeks (n = 162) and 2) usual care (n = 157). Demographics, diagnoses and medication use were retrieved from medical records, and baseline cognition, functioning, HRQoL, loneliness and psychological wellbeing were assessed. Primary trial outcomes will be participants’ loneliness (De Jong Giervald Loneliness Scale) and HRQoL (15D).

Results

The mean age of participants was 83 years, 73% were female and mean Minimental State Examination of 21 points. The participants were living with multiple co-morbidities and/or disabilities. The intervention and control groups were comparable at baseline. The adherence with intervention was moderate, with a mean attendance of 6.8 out of the nine sessions. Of the participants, 14% refused, fell ill or were deceased, and therefore, participated three sessions or less. General subjective alleviation of loneliness was achieved in 57% of the intervention participants. Of the respondents, 96% would have recommended a respective group intervention to other older adults. Intervention participants appreciated their nature excursions and experiences.

Conclusions

We have successfully randomised 319 lonely residents in assisted living facilities into a trial about the effects of nature experiences in a group-format. The feedback from participants was favourable. The trial will provide important information about possibilities of alleviating loneliness with peer-related nature-based experiences in frail residents.

Trial registration

ClinicalTrials.gov, ID: NCT05507684. Registration 19/08/2022.
Associations between clinical data, vaccination status, antibody responses, and post-COVID-19 symptoms in Thais infected with SARS-CoV-2 Delta and Omicron variants: a 1-year follow-up study
Authors: Khongsiri Wathusiri , Poolchanuan Prapassorn , Dulsuk Adul , Thippornchai Narin , Phunpang Rungnapa , Runcharoen Chakkaphan , Boonprakob Thitiya , Hemtong Onura , Chowplijit Suchada , Chuapaknam Vachara , Siripoon Tanaya , Piyaphanee Watcharapong , Luvira Viravarn , Rotejanaprasert Chawarat , Leaungwutiwong Pornsawan , Chantratita Wasun , Chantratita Narisara , Kosoltanapiwat Nathamon
Published: October 2024

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), led to a global pandemic from 2020. In Thailand, five waves of outbreaks were recorded, with the fourth and fifth waves driven by the Delta and Omicron variants, resulting in over 20,000 new confirmed cases daily at their peaks.

Methods

This cross-sectional study investigated the associations between clinical symptoms, vaccination status, antibody responses, and post-COVID-19 sequelae in COVID-19 patients. Plasma samples and clinical data were collected from participants admitted to hospitals in Thailand between July 2021 and August 2022, with follow-ups conducted for one year. The study included 110 participants infected with either the Delta (n = 46) or Omicron (n = 64) variants. Virus genotypes were confirmed by RT-PCR of nasal swab RNA and partial nucleotide sequencing of the S gene. IgG and IgA antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 Delta and Omicron variants were measured in plasma samples using ELISA.

Results

Pneumonia was found to be associated with Delta variant infections, while sore throat, congestion or runny nose, and headache were linked to Omicron infections. Vaccination with fewer than two doses and diabetes mellitus were significantly associated with higher disease severity. Specific IgG and IgA antibodies against the RBD of the Delta variant generally rose by day 14 and were maintained for up to two months, whereas the pattern of antibody response to the Omicron variant was less clear. Antibody risings were found to be positively associated with pneumonia, certain underlying conditions (obesity, hypertension, dyslipidemia, and diabetes mellitus), and age ≥ 60 years. Delta variant infections were associated with forgetfulness, hair loss, and headache during the 1-year post-infection period. Females were more likely to experience hair loss, forgetfulness, and joint pain, while older age was associated with joint pain.

Conclusions

This study enhances our understanding of SARS-CoV-2 infections in Thais, particularly concerning the Delta and Omicron variants. The findings can inform public health planning and response strategies for future outbreaks of SARS-CoV-2 or other emerging viral diseases.