bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of Hematology/Oncology Program Leaders on Equity and Global Health Opportunities for Fellows
Authors: Falade Ayo S. , Hornstein Paula R. , Slater Sarah E. , Triedman Scott A. , Buswell Lori A. , Fadelu Temidayo A.
Published: August 2024

PURPOSE

The study assesses the current state of global oncology (GO)/hematology training opportunities in US fellowship programs.

METHODS

We developed a comprehensive survey of 64-Likert multiple-choice and open-ended questions. The survey was electronically distributed to fellowship program leaders at Accreditation Council for Graduate Medical Education-accredited adult hematology/oncology fellowships. Program directors received three reminders after which survey was sent to assistant program directors or division heads for programs not represented.

RESULTS

A total of 171 programs were eligible for the survey. We received 42 (24.6%) responses; 40 were included in the analysis, and two were excluded for declined consent and incomplete responses. The programs include large academic (81.6%) and community hospitals (10.5%). Of the respondents, 18 (48.6%) reported offering some opportunities for global health training, and half reported interest among current fellows. Most programs (29, 82.9%) had three or fewer faculty engaged in GO research. Institutional training grants were available in 15 (39.5%) programs, of which six (40%) allowed for global health research. Of the 18 programs offering global health training activities, most (15, 83.3%) report less than a quarter of their trainees currently participate in GO experiences. The most commonly perceived barriers to GO opportunities include competing priorities (85.3%) and lack of faculty mentors with GO-related experience (82.4%). Conversely, the most commonly perceived facilitators include established partnerships outside the United States (97.0%) and dedicated institutional funding (93.9%).

CONCLUSION

Our survey demonstrates that although there is significant interest among fellowship trainees, a minority of the fellowship programs offer GO opportunities. Providing GO opportunities would require programs to establish partnerships with institutions outside the United States and to have systematic approaches of addressing other barriers, including enhancing funding and mentorship.
Danuglipron – an innovate GLP agonist - literature short review
Authors: Frańczuk Agata , Szpulak Angelika , Kopczyńska Ewelina , Makłowicz Aleksandra , Kuleta Katarzyna , Głoskowska Julia , Grzelka Michalina , Słychan Katarzyna , Głuszczyk Agnieszka , Plizga Jakub
Published: August 2024

Obesity and type 2 diabetes mellitus (T2DM) are global health problems with increasing prevalence, associated with numerous metabolic, cardiovascular and renal complications(1,2). Current treatments include GLP-1 receptor agonists (GLP-1RAs), which have shown benefits in weight reduction and glycaemic control. Danuglipron, a novel, oral, small-molecule GLP-1RA, is being investigated for its efficacy in treating these conditions. The novel oral method of administration may contribute to an increase in its regularity of use among patients who find systematic use of injections difficult. The aim of our study is to describe this new drug, its' mechanism of action and discuss possible benefits versus adverse effects.
Obesity and type 2 diabetes mellitus (T2DM) represent significant global health challenges with a rising prevalence, linked to a multitude of metabolic, cardiovascular, and renal complications. Current therapeutic approaches encompass GLP-1 receptor agonists (GLP-1RAs), which have exhibited favorable outcomes in weight management and glycemic regulation. Danuglipron, an innovative oral small-molecule GLP-1RA, is undergoing investigation for its effectiveness in addressing these conditions. The unique oral delivery method could potentially enhance its adherence among patients encountering difficulties with routine injections. Our study aims to delineate this novel medication, elucidate its mechanism of action, and deliberate on the prospective benefits versus drawbacks.
Physical activity in diabetic nephropathy-protective and preventive effects on the occurrence of diabetic complications
Authors: Poborowska Dominika , Kahan Weronika , Szafrańska Weronika , Polańska Katarzyna , Wojaczek Marta , Niedbał Piotr , Kosińska Agnieszka , Kras Magdalena , Lelek Katarzyna , Łata Marcin
Published: August 2024

Introduction and purpose
Nephropathy is characterized by a gradual increase in blood pressure, urinary albumin excretion and cardiovascular risk. It is associated with a decrease in glomerular filtration rate (GFR) resulting in end-stage renal failure. It lowers the standard of living and leads to premature death in patients with this complication of diabetes. The purpose of this article is to present the problem of diabetic nephropathy, possible diagnostic methods, treatment methods with emphasis on the effect of physical activity on improving and alleviating diabetic nephropathy.  
State of knowledge
This article reviews the literature on type 1 and type 2 diabetes, diabetic complications with special attention to diabetic nephropathy and the effect of exercise on the frequency and progression of this complication. The number of people with diabetes and the associated complications of diabetes are steadily increasing. Proper diet and physical activity can maintain normal blood glucose levels and slow the progression of diabetic nephropathy as well as other diabetic complications. 
Material and method
The literature available in “PubMed” and Google Schoolar was reviewed. The focus was on the problem of complications of diabetes mellitus with a special emphasis on diabetic nephropathy, pathogenesis, diagnosis, treatment methods and prevention of nephropathy through the beneficial effects of exercise in diabetic patients. 
Summary
In our review, we managed to show how diabetic nephropathy is a big problem in diabetic patients. Based on a number of studies, we were able to prove the beneficial effects of physical activity on reducing the incidence of diabetes complications. Through a variety of modalities and mechanisms, exercise helps control blood sugar and blood pressure and reduce serum creatinine and albuminuria, thereby alleviating kidney damage.
Injections for weight loss: what’s new in GLP-1 RAs for obesity treatment – review
Authors: Zając Małgorzata Maria , Zaucha Radosław , Silldorff Julia , Anczyk Stanisław , Dudek Marcin , Fura Tomasz , Felińska Zuzanna , Iszczuk Oliwia , Gajkiewicz Magdalena , Jaskółka Magdalena
Published: August 2024

Among the myriad challenges confronting contemporary medicine, the obesity epidemic stands out as one of the most critical, warranting special attention due to its association with numerous severe comorbidities and its significant consumption of both human lives and financial resource. This review presents recent clinical trials addressing the issue of the effects of Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs) in the management of overweight and obesity in non-diabetic patients and identifies areas requiring further investigation.
GLP-1 RAs, initially used in the treatment of type II diabetes, represent some of the most promising pharmacotherapeutic agents for obesity. Their mechanism of action involves lowering glucose levels by stimulating insulin secretion, inhibiting glucagon secretion, and delaying gastric emptying. They also affect the centres of hunger and satiety, contributing to a reduction in food intake, including food cravings. In clinical studies, GLP-1 RAs have demonstrated effectiveness in reducing body weight in both diabetic and non-diabetic patients with fairly good tolerance. The discussion is grounded in three clinical studies that examine the use of liraglutide and semaglutide, and the development of a novel GLP-1 RA, ecnoglutide.
The use of semaglutide and liraglutide is associated with significant weight reduction and a decrease in cardiovascular risk in non-diabetic patients, while ecnoglutide represents a promising new GLP-1 RA that requires further investigation.
Effects of Oral Collagen Supplementation on Skin Aging
Authors: Marzec Weronika Zofia , Marzec Marcelina Teresa , Łakoma Aleksandra , Wydra-Rojek Aleksandra , Marszałek Anna , Kutyła Katarzyna , Mokot Wojciech Jan , Wasiewicz-Ciach Paulina , Kuczyński Piotr , Choiński Maciej
Published: August 2024

This systematic review evaluates the effects of oral collagen supplementation on skin hydration, elasticity, and wrinkle reduction. Collagen, a key protein in the skin, decreases with age, causing visible signs of aging. The review synthesizes findings from 31 articles, including randomized controlled trials, systematic reviews, and meta-analyses, focusing on the efficacy of hydrolyzed collagen (HC), collagen tripeptides (CP), and low molecular weight collagen peptides (LMWCP). The review also highlights collagen peptides' role in stimulating collagen synthesis, improving skin barrier function, and promoting hydration. Despite some limitations, the evidence supports collagen supplements, as a non-invasive option for improving skin health. 
 
Aim of the Study
The study aims to evaluate the impact of oral collagen supplementation, particularly hydrolyzed collagen (HC), collagen tripeptides (CP), and low molecular weight collagen peptides (LMWCP), on improving skin hydration, elasticity, and wrinkle reduction.
 
Materials and methods
A  review  of  the  literature  collected  in  the PubMed  database  was  performed  to  gather information found under the key words “collagen supplementation," "skin aging," "hydrolyzed collagen," "collagen peptides," "skin hydration," "skin elasticity," and "wrinkle reduction."
The management of acute complete ruptures of the ulnar collateral ligament of the thumb
Authors: Mikhail Mark , Riley Nicholas , Rodrigues Jeremy , Carr Elaine , Horton Robin , Beale Nicholas , Beard David J. , Dean Benjamin J. F.
Published: August 2024

Aims

Complete ruptures of the ulnar collateral ligament (UCL) of the thumb are a common injury, yet little is known about their current management in the UK. The objective of this study was to assess the way complete UCL ruptures are managed in the UK.

Methods

We carried out a multicentre, survey-based cross-sectional study in 37 UK centres over a 16-month period from June 2022 to September 2023. The survey results were analyzed descriptively.

Results

A total of 37 centres participated, of which nine were tertiary referral hand centres and 28 were district general hospitals. There was a total of 112 respondents (69 surgeons and 43 hand therapists). The strongest influence on the decision to offer surgery was the lack of a firm ‘endpoint’ to stressing the metacarpophalangeal joint (MCPJ) in either full extension or with the MCPJ in 30° of flexion. There was variability in whether additional imaging was used in managing acute UCL injuries, with 46% routinely using additional imaging while 54% did not. The use of a bone anchor was by far the most common surgical option for reconstructing an acute ligament avulsion (97%, n = 67) with a transosseous suture used by 3% (n = 2). The most common duration of immobilization for those managed conservatively was six weeks (58%, n = 65) and four weeks (30%, n = 34). Most surgeons (87%, n = 60) and hand therapists (95%, n = 41) would consider randomizing patients with complete UCL ruptures in a future clinical trial.

Conclusion

The management of complete UCL ruptures in the UK is highly variable in certain areas, and there is a willingness for clinical trials on this subject.

Cite this article: Bone Jt Open 2024;5(8):708–714.
Cleaning Performance Evaluation of Pneumatic Spray Delivery Based Solid Set Canopy Delivery System
Authors: Mozzanini Eric , Bhalekar Dattatray G. , Grella Marco , Hoheisel Gwen-Alyn , Samy Shar , Balsari Paolo , Gioelli Fabrizio , Khot Lav R.
Published: August 2024

Highlights

Ad hoc methodology was assessed to evaluate the Pneumatic Spray Delivery-Solid Set Canopy Delivery System (PSD-SSCDS) cleaning performance.

Evaluated were the five viable cleaning techniques including air injection and water rinse.

System performance meets the ISO16119-4 internal cleaning requirements.

Among tested methods, water rinse was the most effective cleaning technique.

Abstract. Solid set canopy delivery system (SSCDS), a fixed spray system variant, has the potential to realize automated and timely spray applications in modern grapevine production systems typical of Washington State in the United States. Optimized SSCDS configurations could be a viable replacement for conventional pesticide application equipment (PAE) and can also help with abiotic stress management. However, SSCDS, as a PAE, should effectively mitigate the risks and environmental impacts associated with pesticide use. This study was thus aimed at evaluating a pneumatic spray delivery (PSD)-SSCDS, first in the laboratory and then under field conditions, to understand system cleaning performance according to a methodology based on the ISO22368-1 (2004) standard for such fixed and semi-mobile sprayers. The cleaning performance was quantified as the percent amount of residue in the SSCDS components after the spray application. A pilot laboratory setup was used to evaluate the PSD-SSCDS component cleaning performance. The system was cleaned using five viable cleaning techniques: air injection for 30 (conventional cleaning technique), 60, 90, and 300 s, and one water rinse after 30 s air injection. The technique that performed best was field evaluated in a large-scale modern grapevine layout. Overall, the use of water to rinse the system component achieved cleaning performance >99.67%. Field trials also demonstrated that the PSD-SSCDS layout was easy to clean through a triple water rinse and capable of meeting the ISO16119-4 (2014) set threshold. Keywords: Fixed spray delivery system, Internal cleaning, Pesticide application equipment, Pesticide residues, Spray application technology.
Linkage between tectonic events in Connemara and the evolution of the South Mayo Trough
Authors: Badley Michael E. , Graham John R. , Leake Bernard Elgey
Published: August 2024

Abstract: The Ordovician sedimentary rocks of the South Mayo Trough in western Ireland represent three different sedimentary basins. A northern basin records the erosion of an uplifted ophiolite that had been emplaced onto the Laurentian margin. A southern basin records the erosion of a volcanic complex rooted on continental crust and has clear sedimentary linkage with Connemara. These two separate basins were juxtaposed along a tectonic structure running through the Erriff Valley before being overlain by a third succession (represented by the Glenummera and Mweelrea formations) that formed due to local extension. The southern succession overlies the Cambro-Ordovician Lough Nafooey Arc rocks that, along with the Laurentian margin, have a strong magnetic signature that can be traced through exposed inliers and beneath the Carboniferous cover to Tyrone. To the northeast of South Mayo, the arc and the Laurentian margin are juxtaposed and the original forearc and hyperextended Laurentian margin is interpreted to have underthrust the main body of Laurentia. Connemara is interpreted to have formed as a detached microcontinental block in similar manner to Slishwood. Preservation of the South Mayo successions is partly due to an original bend in the Laurentian margin and partly to strike-slip and rotation of Connemara during the later stages of the Grampian orogeny.
The 'Zygous Rule' applied to Blastozoan basal plates
Authors: Paul Christopher R.C.
Published: August 2024

Abstract: Application of the terms 'zygous' (Greek: a yoke or pair) and 'azygous' to blastozoan basal plates implies that larger, zygous, basals represent two original plates. This idea, here called the 'zygous rule', seems sensible because zygous basals only occur in taxa with fewer than five basal plates. In all normal blastoids, coronates and glyptocystitoid rhombiferans, counting zygous basals as two plates gives the expected 'zygous sum' of five and implies that these taxa were derived from an ancestor with five, equal basals. Hemicosmitoid rhombiferans give a zygous sum of six and anomalous blastoids with three or four radial plates above the basals often give zygous sums of three or four. Thus, an alternative interpretation of zygous basals is that they are a geometrical necessity of fitting fewer than five basals against the plates above without gaps. The 'zygous rule' predicts that zygous basals should subtend 144°, and azygous basals 72°. Basal views of various blastozoans show that examples which do not correspond to this prediction are much more common than those which do. Basals are usually equally spaced around the stem facet. The number of basals in blastozoans may carry more phylogenetic significance than expected.
Botanists and Antiquaries in the Garden of the Hesperides
Authors: Mason Peter
Published: August 2024

Abstract: The first recorded instance of the extinction of a plant species through human intervention is that of the Libyan silphium, the last stalk of which was believed to have been presented to the emperor Nero in the first century ce. It took the concerted work of antiquaries and botanists to unravel just what had happened. This contribution highlights the role played by Antonio Agustín in his work on ancient coins, among which the image of silphium was preserved on coins from Cyrene in Libya. The scientific debates of sixteenth-century botanists (Andrés Laguna, Pietro Andrea Mattioli, and others) came to rely, in this case, on the patient scrutiny of the experts on ancient coins.
Chaucerian Ekphrasis: Craft, Intertext, Dispence
Authors: Jones Mike Rodman
Published: August 2024

Abstract: Ekphrasis has long been a topic of interest to literary scholars, but until quite recently medieval ekphrasis has existed on the periphery of most accounts of it. This article explores the distinctive nature of medieval ekphrasis in passages of description in the Middle English poetry of Geoffrey Chaucer. It argues that Middle English poetry was underpinned by a poetics of craft which made later ekphrastic theorisations, especially the concept of the 'paragone'—the confrontation of the arts, especially poetry and painting—problematic. It argues that Chaucer uses ekphrasis as a type of intertextual visualisation, a way of recognising, acknowledging, but also adapting and reworking intertextual materials. Lastly, it argues that Chaucerian ekphrasis worked to foreground the socio-economics of cultural production. By placing Chaucer's ekphrasis in comparison with a near contemporary passage of satirical ekphrastic description in the alliterative tradition, it becomes clear that Chaucer's ekphrasis works to emphasise the centrality of patronage in the creation of both visual and verbal art.
Textu(r)al Performances of Affect in John Donne's Valediction Poems
Authors: Riedelsheimer Martin
Published: August 2024

Abstract: This article suggests a method of 'differential' reading—that is, reading for the affective surplus beyond a text's semantics—in order to analyse the role of affect in John Donne's poetry. Derived from contrasting several twenty-first-century theories of affect (Massumi, Sedgwick, Brinkema), such a differential reading wants to explore the way in which affect is expressed through poetic form and through the more immediately experiential, or material, dimensions of a poem: that is, through its texture. Donne's valediction poems make use both of their evocation of a concrete materiality that affords touching and being touched and of their creation of cognitive intensity through semantic overdetermination to perform affect in their poetic language, allowing for affective experience and cognitive reading to merge in a blend of thinking and feeling.
Photonic generation and programmable switching of variable-band chirped waveforms with immunity to power fading
Authors: Yang Shuna , Qin Xu , Yang Bo , Chi Hao
Published: August 2024

A photonic approach for generating and programmable switching variable-band chirped waveforms by using a dual-parallel Mach–Zehnder modulator (DPMZM) is proposed and experimentally demonstrated. By coupling binary switching codes with the baseband chirped signal and applying them into the RF input port of DPMZM, the variable-band chirped waveforms can be generated and fast switched. The switching speed is consistent with the input code bit rate. Moreover, by properly adjusting the bias voltages, the generated signals can be anti-dispersion transmitted over different distances. Full experimental verification on the generation and programmable switching of the chirped waveforms centered at 2.1, 6.3, and 8.4 GHz or 1.5, 4.5, and 6 GHz over 10 or 20 km standard single-mode fibers with 4 or 100 Mbps switching rates are successfully carried out. The proposed approach features compact architecture, programmable switching capability and immunity to power fading, which are significant in distributed multifunction radar networks with optical fiber-based transmission.
Miniaturized quasi-BICs based on a two-dimensional heterostructure to realize a low-threshold nanolaser
Authors: Qian Linyong , Zhang Xin , Zhang Jiahua , Yang Zhengweiyi , Qiu Yun , Wang Kangni
Published: August 2024

Bound states in the continuum (BICs) have been demonstrated as an effective mechanism to achieve high quality (Q)-factor cavities for nanolasers. However, the development of a compact BIC laser with a low threshold has remained elusive. Here, we numerically report lasing action from symmetry-protected BICs in a two-dimensional heterostructure, which consists of compound gratings with finite cells surrounded by orthogonal distributed Bragg reflectors (DBRs). The compound grating is used to excite quasi-BIC resonance with a high Q-factor, and DBRs enable light confinement and localized electric fields to enhance light–matter interaction. The nanolaser with a threshold of 16.8 µJ/cm2 is achieved within a footprint as small as 3.35 × 3.35 µm2. By changing the phase adjusting gap or asymmetry degree, it is possible to control the lasing emission. This work reveals a new, to our knowledge, path toward compact BIC lasers with a simple scheme for applications that require a small footprint and low threshold.
Applied artificial intelligence for global child health: Addressing biases and barriers
Authors: Muralidharan Vijaytha , Schamroth Joel , Youssef Alaa , Celi Leo A. , Daneshjou Roxana
Published: August 2024

Given the potential benefits of artificial intelligence and machine learning (AI/ML) within healthcare, it is critical to consider how these technologies can be deployed in pediatric research and practice. Currently, healthcare AI/ML has not yet adapted to the specific technical considerations related to pediatric data nor adequately addressed the specific vulnerabilities of children and young people (CYP) in relation to AI. While the greatest burden of disease in CYP is firmly concentrated in lower and middle-income countries (LMICs), existing applied pediatric AI/ML efforts are concentrated in a small number of high-income countries (HICs). In LMICs, use-cases remain primarily in the proof-of-concept stage. This narrative review identifies a number of intersecting challenges that pose barriers to effective AI/ML for CYP globally and explores the shifts needed to make progress across multiple domains. Child-specific technical considerations throughout the AI/ML lifecycle have been largely overlooked thus far, yet these can be critical to model effectiveness. Governance concerns are paramount, with suitable national and international frameworks and guidance required to enable the safe and responsible deployment of advanced technologies impacting the care of CYP and using their data. An ambitious vision for child health demands that the potential benefits of AI/Ml are realized universally through greater international collaboration, capacity building, strong oversight, and ultimately diffusing the AI/ML locus of power to empower researchers and clinicians globally. In order that AI/ML systems that do not exacerbate inequalities in pediatric care, teams researching and developing these technologies in LMICs must ensure that AI/ML research is inclusive of the needs and concerns of CYP and their caregivers. A broad, interdisciplinary, and human-centered approach to AI/ML is essential for developing tools for healthcare workers delivering care, such that the creation and deployment of ML is grounded in local systems, cultures, and clinical practice. Decisions to invest in developing and testing pediatric AI/ML in resource-constrained settings must always be part of a broader evaluation of the overall needs of a healthcare system, considering the critical building blocks underpinning effective, sustainable, and cost-efficient healthcare delivery for CYP.
Interventions to reduce leprosy related stigma: A systematic review
Authors: Willis Matthew , Fastenau Anil , Penna Srilekha , Klabbers Gonnie
Published: August 2024

Stigmatisation is a major issue faced by those affected by leprosy globally. Reducing stigmatisation encourages care seeking behaviour to occur earlier and can help reduce harm and spread of leprosy. This systematic literature review aimed to summarise what effective stigma reducing interventions exist for leprosy, and as a secondary question explore what evidence exists regarding their cost. A systematic literature review was conducted. Three databases–PubMed, Embase and Web of science–were searched using the search terms “leprosy”, “interven*”, “reduc*”, and “stigma*”.Seventeen publications were eligible for inclusion in the review. The current manuscript identified interventions under 6 main categories (i) Information, education, and communication (IEC) (ii) community led projects, (iii) Socioeconomic rehabilitation, (iv) mixed interventions, (v) integration of leprosy within the health system and (vi) Cosmetic or surgical care. Specific evidence regarding cost was only provided by one out of the seventeen papers. Multiple interventions were shown to successfully reduce leprosy related stigma, however, information on their cost is not readily available. The evidence uncovered by this review is restricted to three Asian countries; Nepal, India and Indonesia. To ensure the success of stigma reduction in leprosy interventions worldwide these interventions need to be tried in other leprosy endemic areas to test their effectiveness across contextual and cultural scenarios.
Clinical sensitivity and time-to-result of a cascaded pooled testing approach for assessing the prevalence and intensity of Schistosoma haematobium infection
Authors: Degarege Abraham , Levecke Bruno , Negash Yohannes , Animut Abebe , Erko Berhanu
Published: August 2024

Background

This study compared the clinical sensitivity and the time-to-result of an individual testing (IT) and a cascaded pooled testing approach (CPT; a positive test result in a pooled sample triggers examination of smaller-sized pools or individual samples) for assessing the prevalence and the intensity of Schistosoma haematobium infection. We also compared the sensitivity of the CPT in detecting S. haematobium infection when deploying urine filtration microscopy (UFM) vs. urine reagent strips (URS), and testing 10 mL vs. 15 mL of urine.

Methodology/Principal findings

Between October 2021 and April 2022, S. haematobium eggs were counted in urine samples collected from school-aged children living in the Afar and Gambella Regional States of Ethiopia. Urine samples were collected at baseline (n = 1,288), and one month after administration of praziquantel (n = 118). All urine samples were processed through both an IT and a CPT approach (pools of 5, 10, 20, and 40 individual samples), deploying UFM (10 mL) and URS (10 mL). In addition, 15 mL urine was processed through the CPT deploying UFM. At baseline, the prevalence of S. haematobium infection estimated when using UFM and deploying a CPT approach was significantly lower (17.3%) compared to an IT approach (31.5%). The clinical sensitivity of the CPT in detecting S. haematobium eggs was 51.7%. The sensitivity increased significantly as a function of increasing log transformed urine egg counts (UECs) of the individual samples (OR 2.71, 95%CI 1.63 ― 4.52). The sensitivity was comparable when the amount of urine examined was 10 mL (51.7%) vs. 15 ml (50.8%), and when UFM was used for testing vs. URS (51.5%). The mean log UECs estimated following the CPT approach was lower compared to the estimate by the IT (p <0.001). UECs of the individual samples estimated using the IT and CPT approaches were moderately correlated (r = 0.59 when 10 mL and 15 mL urine was examined after pooling). CPT reduced the time needed for processing urine samples and testing for S. haematobium infection by 29% with UFM and by 27.7% with URS.

Conclusions/Significance

CPT based on UFM and URS techniques may help to rapidly identify areas with higher prevalence of S. haematobium infection (hotspots) in a population. However, the performance of this approach in estimating the prevalence of infection may be compromised, particularly in endemic areas with low intensity infection.
Carvedilol suppresses ryanodine receptor-dependent Ca2+ bursts in human neurons bearing PSEN1 variants found in early onset Alzheimer’s disease
Authors: Hori Atsushi , Inaba Haruka , Hato Takashi , Tanaka Kimie , Sato Shoichi , Okamoto Mizuho , Horiuchi Yuna , Paran Faith Jessica , Tabe Yoko , Mori Shusuke , Rosales Corina , Akamatsu Wado , Murayama Takashi , Kurebayashi Nagomi , Sakurai Takashi , Ai Tomohiko , Miida Takashi
Published: August 2024

Seizures are increasingly being recognized as the hallmark of Alzheimer’s disease (AD). Neuronal hyperactivity can be a consequence of neuronal damage caused by abnormal amyloid β (Aß) depositions. However, it can also be a cell-autonomous phenomenon causing AD by Aß-independent mechanisms. Various studies using animal models have shown that Ca2+ is released from the endoplasmic reticulum (ER) via type 1 inositol triphosphate receptors (InsP3R1s) and ryanodine receptors (RyRs). To investigate which is the main pathophysiological mechanism in human neurons, we measured Ca2+ signaling in neural cells derived from three early-onset AD patients harboring Presenilin-1 variants (PSEN1 p.A246E, p.L286V, and p.M146L). Of these, it has been reported that PSEN1 p.A246E and p.L286V did not produce a significant amount of abnormal Aß. We found all PSEN1-mutant neurons, but not wild-type, caused abnormal Ca2+-bursts in a manner dependent on the calcium channel, Ryanodine Receptor 2 (RyR2). Indeed, carvedilol, an RyR2 inhibitor, and VK-II-86, an analog of carvedilol without the β-blocking effects, sufficiently eliminated the abnormal Ca2+ bursts. In contrast, Dantrolene, an inhibitor of RyR1 and RyR3, and Xestospongin c, an IP3R inhibitor, did not attenuate the Ca2+-bursts. The Western blotting showed that RyR2 expression was not affected by PSEN1 p.A246E, suggesting that the variant may activate the RyR2. The RNA-Seq data revealed that ER-stress responsive genes were increased, and mitochondrial Ca2+-transporter genes were decreased in PSEN1A246E cells compared to the WT neurons. Thus, we propose that aberrant Ca2+ signaling is a key link between human pathogenic PSEN1 variants and cell-intrinsic hyperactivity prior to deposition of abnormal Aß, offering prospects for the development of targeted prevention strategies for at-risk individuals.
Sustainable agility of product development process based on a rough cloud technique: A case study on China’s small and medium enterprises
Authors: Zhao Zhining , Alli Hassan , Ahmadipour Masoud , Che me Rosalam
Published: August 2024

The importance of incorporating an agile approach into creating sustainable products has been widely discussed. This approach can enhance innovation integration, improve adaptability to changing development circumstances, and increase the efficiency and quality of the product development process. While many agile methods have originated in the software development context and have been formulated based on successful software projects, they often fail due to incorrect procedures and a lack of acceptance, preventing deep integration into the process. Additionally, decision-making for market evaluation is often hindered by unclear and subjective information. Therefore, this study introduces an extended TOPSIS (Technique for Order Performance by Similarity to Ideal Solution) method for sustainable product development. This method leverages the benefits of cloud model theory to address randomness and uncertainty (intrapersonal uncertainty) and the advantages of rough set theory to flexibly handle market demand uncertainty without requiring extra information. The study proposes an integrated weighting method that considers both subjective and objective weights to determine comprehensive criteria weights. It also presents a new framework, named Sustainable Agility of Product Development (SAPD), which aims to evaluate criteria for assessing sustainable product development. To validate the effectiveness of this proposed method, a case study is conducted on small and medium enterprises in China. The obtained results show that the company needs to conduct product structure research and development to realize new product functions.
Can trusted authorities change minds on anti-LGBTQ norms: Evidence from an experiment in Ghana
Authors: Yekple Michael , Mitkov Zlatin
Published: August 2024

Across numerous African societies, a prevalent resistance to LGBTQ rights is evident. While prominent strides have been made on LGBTQ rights in various parts of the world, the African context has witnessed limited progress. Public opinion polls indicate that influential figures have succeeded in altering public sentiment towards LGBTQ rights in Western countries, yet such progress remains elusive in the African context. Mechanisms effective in shifting public attitudes toward embracing LGBTQ rights remain largely unexplored, especially in the African context. In this paper, we consider whether endorsement messages conveyed by trusted authorities possess the potential to foster a shift in attitudes towards embracing LGBTQ rights among a nationally representative sample of respondents in Ghana. Through a factorial experiment, we find that there are varying impacts of messaging from distinct trusted authorities in shaping attitudes toward embracing LGBTQ rights. Notably, pro-LGBTQ messaging from traditional and co-partisan leaders yields modest effects, while messaging from religious leaders exhibits no discernible impact. These findings hold significance for determining strategic focal points in potential endeavors to advance LGBTQ rights within the African context.
Speech sensorimotor relationships in francophone preschoolers and adults: Adaptation to real-time auditory feedback perturbations
Authors: Trudeau-Fisette Paméla , Vidou Camille , Ménard Lucie
Published: August 2024

Purpose

This study investigates the development of sensorimotor relationships by examining adaptation to real-time perturbations of auditory feedback.

Method

Acoustic signals were recorded while preschoolers and adult speakers of Canadian French produced several utterances of the front rounded vowel /ø/ for which F2 was gradually shifted up to a maximum of 40%.

Results

The findings indicate that, although preschool-aged children produced overall similar responses to the perturbed feedback, they displayed significantly more trial-to-trial variability than adults. Furthermore, whereas the magnitude of the adaptation in adults was positively correlated with the slope of the perceptual categorical function, the amount of adaptation in children was linked to the variability of their productions in the baseline condition. These patterns suggest that the immature motor control observed in children, which contributes to increased variability in their speech production, plays a role in shaping adaptive behavior, as it allows children to explore articulatory/acoustic spaces and learn sensorimotor relationships.
CagA toxin and risk of Helicobacter pylori-infected gastric phenotype: A meta-analysis of observational studies
Authors: Naing Cho , Aung Htar Htar , Aye Saint Nway , Poovorawan Yong , Whittaker Maxine A.
Published: August 2024

Background

Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region.

Methods

Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders.

Results

Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73–91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67–90%) in H. pylori-infected gastritis, 86% (95%CI = 73–96%) in peptic ulcer disease, and 83% (95%CI = 51–100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15–5.55).

Conclusion

Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease.
An approach for developing a blood-based screening panel for lung cancer based on clonal hematopoietic mutations
Authors: Anandakrishnan Ramu , Shahidi Ryan , Dai Andrew , Antony Veneeth , Zyvoloski Ian J.
Published: August 2024

Early detection can significantly reduce mortality due to lung cancer. Presented here is an approach for developing a blood-based screening panel based on clonal hematopoietic mutations. Animal model studies suggest that clonal hematopoietic mutations in tumor infiltrating immune cells can modulate cancer progression, representing potential predictive biomarkers. The goal of this study was to determine if the clonal expansion of these mutations in blood samples could predict the occurrence of lung cancer. A set of 98 potentially pathogenic clonal hematopoietic mutations in tumor infiltrating immune cells were identified using sequencing data from lung cancer samples. These mutations were used as predictors to develop a logistic regression machine learning model. The model was tested on sequencing data from a separate set of 578 lung cancer and 545 non-cancer samples from 18 different cohorts. The logistic regression model correctly classified lung cancer and non-cancer blood samples with 94.12% sensitivity (95% Confidence Interval: 92.20–96.04%) and 85.96% specificity (95% Confidence Interval: 82.98–88.95%). Our results suggest that it may be possible to develop an accurate blood-based lung cancer screening panel using this approach. Unlike most other “liquid biopsies” currently under development, the approach presented here is based on standard sequencing protocols and uses a relatively small number of rationally selected mutations as predictors.
Hemodynamic differences determining rupture and non-rupture in middle cerebral aneurysms after growth
Authors: Nishiwaki Takayuki , Ikedo Taichi , Kushi Yuji , Shimonaga Koji , Kobayashi Hiroki , Itazu Takaaki , Otsuka Ryotaro , Tega Jota , Hamano Eika , Imamura Hirotoshi , Mori Hisae , Nakamura Masanori , Kato Takayuki , Shirakami Shinichi , Iihara Koji , Iwama Toru , Kataoka Hiroharu
Published: August 2024

Background and purpose

Intracranial aneurysm growth is a significant risk factor for rupture; however, a few aneurysms remain unruptured for long periods, even after growth. Here, we identified hemodynamic features associated with aneurysmal rupture after growth.

Materials and methods

We analyzed nine middle cerebral artery aneurysms that grew during the follow-up period using computational fluid dynamics analysis. Growth patterns of the middle cerebral artery aneurysms were divided into homothetic growth (Type 1), de novo bleb formation (Type 2), and bleb enlargement (Type 3). Hemodynamic parameters of the four ruptured aneurysms after growth were compared with those of the five unruptured aneurysms.

Results

Among nine aneurysms (78%), seven were Type 1, one was Type 2, and one was Type 3. Three (43%) Type 1 aneurysms ruptured after growth. Maximum oscillatory shear index after aneurysmal growth was significantly higher in ruptured Type 1 cases than in unruptured Type 1 cases (ruptured vs. unruptured: 0.455 ± 0.007 vs. 0.319 ± 0.042, p = 0.003). In Type 1 cases, a newly emerged high-oscillatory shear index area was frequently associated with rupture, indicating a rupture point. Aneurysm growth was observed in the direction of the high-pressure difference area before enlargement. In Types 2 and 3 aneurysms, the maximum oscillatory shear index decreased slightly, however, the pressure difference values remain unchanged. In Type 3 aneruysm, the maximum OSI and PD values remained unchanged.

Conclusions

This study suggests that hemodynamic variations and growth pattern changes are crucial in rupture risk determination using computational fluid dynamics analysis. High-pressure difference areas may predict aneurysm enlargement direction. Additionally, high maximum oscillatory shear index values after enlargement in cases with homothetic growth patterns were potential rupture risk factors.
Cross-relationship between COVID-19 infection and anti-obesity products efficacy and incidence of side effects: A cross-sectional study
Authors: El-Mezayen Nesrine S. , Abelrazik Yasser R. , Khalifa Dina M. , Dorbouk Nada M. , Moaaz Mai A. , Ali Merna M. , Evy Alaa G. , Mohamed Elshaimaa G. , Abdelhadi Ahmed M. , Adly Irinie , Shams Nilly A.
Published: August 2024

Background

Obesity and COVID-19 are at the top of nowadays health concerns with significant crosstalk between each other. The COVID-19 pandemic negatively affected healthy lifestyles and increased obesity prevalence. Thus, there was a surge in anti-obesity products (AOPs) intake. Herein, we evaluated how the pandemic has affected slimming products’ efficacy and safety in patients seeking weight reduction at an urban, weight management centre in Alexandria, Egypt. In addition, the effect of AOPs on COVID-19 infection severity was also appraised to detect whether AOPs can alter COVID-19 host cell entry and infective mechanisms, and thus, affect infection severity.

Methods

Patients were invited to complete an anonymous survey. The survey assessed self-reported changes in weight, the use of AOPs during the COVID-19 pandemic, COVID-19 infection severity, AOPs efficacy, and incidence of side effects. Inclusion criteria were obese patients above 18 years old who got infected by COVID-19 while receiving a single-ingredient AOP.

Results

A total of 462 participants completed our anonymous validated questionnaire. Most of the participants were females (450; 98.4%) with BMI ranging from 24.98–58.46. Eligible participants were only 234 and the top-administered products were orlistat, liraglutide, metformin, green tea, cinnamon, Garcinia cambogia, and Gymnema Sylvestre. In most cases, AOPs intake was beneficial for COVID-19 infection, and most patients experienced mild-to-moderate COVID-19 symptoms. On the other hand, SARS-CoV-2 significantly interferes with AOPs’ mechanisms of action which positively or negatively influences their efficacy and side effects incidence due to predictable pharmacological link.

Conclusion

Concurrent AOPs intake with COVID-19 infection is a two-sided weapon; AOPs attenuate COVID-19 infection, while SARS-CoV-2 interferes with efficacy and side effects incidence of AOPs.
Timeliness and accuracy of the 7-Item Japan Urgent Stroke Triage (JUST-7) score, a prehospital stroke triage tool, assessed by emergency medical services
Authors: Nishiwaki Takayuki , Enomoto Yukiko , Egashira Yusuke , Matsubara Hirofumi , Hori Takamitsu , Sasaki Nozomi , Yoshida Takahiro , Nakayama Noriyuki , Ohe Naoyuki , Ogura Shinji
Published: August 2024

The prompt initiation of stroke treatment significantly influences patient outcomes, highlighting the crucial role of prehospital triage. This study aimed to assess the implementation of the 7-Item Japan Urgent Stroke Triage (JUST-7) score by emergency medical services (EMS) in our region and its effect on emergency transportation for suspected stroke patients. Data were collected from patients suspected of having an acute stroke with a Cincinnati Prehospital Stroke Scale (CPSS) score of 1 or more who were transferred by ambulance within 24 h of symptom onset. Two prehospital stroke scales were employed during different periods: period 1 with CPSS alone (January to December 2020) and period 2 with both CPSS and JUST-7 (January 2021 to March 2023). On-scene time data were obtained from the EMS crews, and data regarding the final diagnosis of patients and their outcomes were obtained from the respective hospitals to which the patients were transferred. These data were compared between periods 1 and 2 and between the CPSS and JUST-7. The results revealed that additional evaluation with JUST-7 did not affect ambulance transport time. The CPSS+JUST-7 approach demonstrated higher specificity in identifying stroke and major artery occlusion than with the CPSS alone; however, an appropriate cut-off value needs to be considered. The JUST-7 achieved a diagnostic concordance rate of 35.9% for the most likely stroke type and 64.0% for the first two most likely types. This research emphasizes the potential of JUST-7 as a valuable addition to prehospital stroke diagnosis protocols. Its flexibility in adapting cut-off values based on regional factors and available medical resources optimizes its utility in diverse healthcare settings. The JUST-7 score is a promising tool for improving patient outcomes through prompt and accurate prehospital assessments.
Microbial L Asparaginases Therapeutic and Industrial Applications
Authors: Acharya Rupa , Bindhani Birendra Kumar , Gupta Nibha
Published: August 2024

L-asparaginase (EC 3.5.1.1) is an enzyme that mostly helps break down asparagine into L-aspartic acid and ammonium in water. This enzyme can be found in many living things, like bacteria, plants, and some animals, like the serum of some rodents. Especially for Acute Lymphoblastic Leukaemia (ALL) and Hodgkin’s lymphoma, it is an important chemotherapeutic drug for treating lymphoproliferative diseases and lymphomas. When L-asparaginase comes in contact with water, it breaks down more easily. At the moment, biotechnological methods using certain microorganisms are mostly used to make L-asparaginase. Still, industrial manufacturing needs a study that focuses on both increasing production yields and coming up with new ways to do things, like using different microbes to make enzymes useful in more situations. This review gives an overview of L-asparaginase’s uses and talks about how it is made by different microbes, as well as its limitations, current research, and issues that need to be fixed before it can be used in industry.