bluuebunny/crossref_metadata_2025 huggingface dataset:
Tuning Lewis Acidity: Design of Titanium Complexes with hemilabile Pyridine‐based Ligands
Authors: Schwitalla Kevin , Gronewold Laura , Schmidtmann Marc , Beckhaus Rüdiger
Published: January 2025

The formation of titanium(IV) complexes with Cp,N,N and Cp,O,N tridentate ligands via insertion of the pyridine‐containing precursors into the pentafulvene moiety of the titanium complexes is reported. After consecutive methylation and treatment with B(C6F5)3 according to a well‐established method, cationic complexes with the weakly coordinating MeB(C6F5)3− anion were obtained. Further introduction of moderately strong coordinating triflato ligands provides insight into the nucleophilicity of the respective pyridinyl ligands. The Lewis acidity of the complexes is determined by well‐established protocols. Depending on the donor strength, the triflato ligand is displaced by the pyridinyl ligand to produce a cationic complex with a triflate anion. The highly Lewis acidic cationic titanium(IV) complexes are able to perform reactions such as H2 functionalization and C−H activation reactions. The additional 15N NMR values of the pyridine‐based ligand and UV/Vis spectra are key features of these ligand systems and further support the coordination mode determination.
Salt Contents in Fermented Dairy Products: A Strategic Blueprint for Healthier Intake
Authors: Massomian Ali , Rashidimehr Azadeh , Mohammadi‐Nasrabadi Fatemeh , Khoshtinat Khadijeh , Esfarjani Fatemeh
Published: January 2025

This study aimed to estimate the quantity and trends of salt intake from industrial fermented dairy products, develop strategies to reduce salt content, and inform policymakers on promoting public health through healthier dairy options. A cross‐sectional study was conducted on fermented dairy products. Seventy‐nine random samples were selected, and the salt (NaCl %) content was determined by potentiometric titration after sample preparation and homogenization; also samples were analyzed for their moisture (oven drying method). Data analysis involved descriptive statistics and one‐sample t‐test. A comprehensive literature review on salt reduction strategies was also performed proposing a model for an optimized low‐salt fermented dairy product. This study found high salt content in many fermented dairy products. Brined cheese had the highest salt level (7.57 g/100 g), while pizza processed cheese had the lowest (1.03 g/100 g). Probiotic yogurts contained less salt (0.29 g/100 g) than regular ones. Other products like doogh (1.04 g/100 g), kefir (0.63 g/100 g), and kashk (2.78 g/100 g) also contributed significantly to salt intake. Most products exceeded recommended salt limits. Consuming just one serving of these products often accounted for a substantial portion of the daily recommended salt intake (WHO: 5 g/day). This research emphasizes the need for reducing salt in fermented dairy products to improve public health. This study highlights the excessive salt content in many fermented dairy products, surpassing recommended daily intake levels. Therefore, to address this public health concern, a multi‐faceted approach is necessary. For this purpose, Policymakers should implement stringent monitoring, enforce food labeling, and develop legislation to reduce salt content. Furthermore, the food industry must innovate to reduce salt while maintaining product quality and taste. On the other hand, consumer education and awareness campaigns are crucial for informed choices. Additionally, further research is needed to understand consumer perceptions and the long‐term impact of salt‐sustainable reduction strategies on dietary habits and public health.
Long‐Term Creatine Supplementation Improves Cognitive and Hippocampal Structural Plasticity Impairments in a D‐Gal‐Induced Aging Model via Increasing CK‐BB Activity in the Brain
Authors: Zhu Zhu , Zhang Hantao , Li Qianlin , Han Xu , Wang Tiantian , Zhang Wenjing , Chen Feiyan , Gu Ling , Yao Qi , Chen Lin , Zhao Yunan
Published: January 2025

Creatine (Cr) is recognized for its role in enhancing cognitive functions through the phosphocreatine (pCr)–creatine kinase system involved in brain energy homeostasis. It is reversibly converted into pCr by creatine kinase (CK). A brain‐specific isoform of CK, known as CK‐BB, is implicated in the brain's energy metabolism. The objective of this research is to ascertain the impact of Cr supplementation on learning and memory skills as well as on structural synaptic plasticity, by modulating CK‐BB. First, we utilized various concentrations of D‐galactose (D‐gal) to create an aging mouse model. Our findings indicated that D‐gal injections at 100 and 1000 mg/kg could lead to cognitive decline, oxidative stress, and damage to structural synaptic plasticity. CK‐BB expression and its activity were reduced at least by approximately 20% in mice injected with 100 and 1000 mg/kg D‐gal compared with control group. Next, an adeno‐associated virus directed against CKB was employed to reduce CK‐BB levels by 34% in the brain. The reduction of CK‐BB in the brain resulted in deficits in learning and memory, oxidative stress, and morphological harm to the hippocampal spines of mice. Finally, the diet of the D‐gal‐induced aging model was enriched with 3% Cr. Mice that received 3% Cr supplementation exhibited a 36% increase in CK‐BB activity and a 14.3% increase in CK‐BB expression following prolonged D‐gal administration. In addition, Cr supplementation mitigated the cognitive impairment, oxidative stress, and hippocampal structural plasticity damage caused by chronic D‐gal injections. Overall, our study revealed that CK‐BB has a critical role in mediating structural plasticity in D‐gal‐induced cognitive impairment. Moreover, it showed that supplementary Cr could serve as a potent neuroprotective substance, preventing or delaying the course of age‐related cognitive deficits.
Multivariable MR Can Mitigate Bias in Two‐Sample MR Using Covariable‐Adjusted Summary Associations
Authors: Gilbody Joe , Borges Maria Carolina , Davey Smith George , Sanderson Eleanor
Published: January 2025

Genome‐wide association studies (GWAS) are hypothesis‐free studies that estimate the association between polymorphisms across the genome with a trait of interest. To increase power and to estimate the direct effects of these single‐nucleotide polymorphisms (SNPs) on a trait GWAS are often conditioned on a covariate (such as body mass index or smoking status). This adjustment can introduce bias in the estimated effect of the SNP on the trait. Two‐sample Mendelian randomisation (MR) studies use summary statistics from GWAS estimate the causal effect of a risk factor (or exposure) on an outcome. Covariate adjustment in GWAS can bias the effect estimates obtained from MR studies conducted using covariate adjusted GWAS data. Multivariable MR (MVMR) is an extension of MR that includes multiple traits as exposures. Here we propose the use of MVMR to correct the bias in MR studies from covariate adjustment. We show how MVMR can recover unbiased estimates of the direct effect of the exposure of interest by including the covariate used to adjust the GWAS within the analysis. We apply this method to estimate the effect of systolic blood pressure on type‐2 diabetes and the effect of waist circumference on systolic blood pressure. Our analytical and simulation results show that MVMR provides unbiased effect estimates for the exposure when either the exposure or outcome of interest has been adjusted for a covariate. Our results also highlight the parameters that determine when MR will be biased by GWAS covariate adjustment. The results from the applied analysis mirror these results, with equivalent results seen in the MVMR with and without adjusted GWAS. When GWAS results have been adjusted for a covariate, biasing MR effect estimates, direct effect estimates of an exposure on an outcome can be obtained by including that covariate as an additional exposure in an MVMR estimation. However, the estimated effect of the covariate obtained from the MVMR estimation is biased.
Assessing Cigarette Reduction Tax‐Effectiveness in Low Tobacco Expenditure Contexts: An Application to Bolivia
Authors: Morales Joaquín , Santander Sara
Published: January 2025

In this research we show that ambitious increases in tobacco tax rates can substantially reduce tobacco consumption, increase fiscal revenue, and provide net positive social benefits even in contexts of low consumption prevalence and intensity. Low nicotine intake still constitutes a grave disease risk factor, and the effectiveness of tax increases might be questioned if income effects are small. We adapt spatial variation of price methodologies to deal with low prevalence and intensity, censored data, and small samples using the Bolivian case as an illustration. We find an average price elasticity of demand of to . Using our estimates of elasticities, we develop a simulation to anticipate the effects of a 35% yearly increase of the Bolivian specific excise on tobacco starting in 2025. Our estimates show that by 2030, this reform could reduce the consumption of cigarettes by 52.6%, diminish the prevalence of smoking by 30.6%, and increase fiscal revenue by $123 million over six years. Moreover, we estimate that the abated direct medical costs of reduced consumption net of the deadweight loss associated with a tax increase would generate a net social gain of over $100 million in five years.
Value‐Based Pricing for Drugs With Uncertain Clinical Benefits
Authors: Jiao Boshen , Hsieh Yuli Lily , Li Meng , Verguet Stéphane
Published: January 2025

Policymakers can use cost‐effectiveness analysis to set value‐based prices (VBP) for new pharmaceuticals. However, the uncertainty of investigational drug benefits complicates this pricing strategy. Such complexity stems from decision‐makers' risk aversion and the potential change in the estimated value with emerging evidence. The recent surge in drugs approved via the Accelerated Approval (AA) pathway in the U.S. has made incorporating uncertainty into VBP crucial. We propose to estimate risk‐adjusted VBP (rVBP) for drugs with uncertain benefits via integrating value of information and expected utility theory. Our approach involves two assessment points: an initial assessment with existing evidence; and a reassessment with new evidence that reduces uncertainty. This approach enables decision‐makers to set rVBP in the initial assessment such that the expected utility, from the exisiting evidence, aligns with the benchmark uncertainty. We evaluate two benchmarks: one with no uncertainty, and one with a decision‐maker's acceptable uncertainty level. We show in a case study of a hypothetical AA drug that rVBP may be lower than traditional VBP, especially under high risk aversion or low acceptable uncertainty. Our methodology adjusts VBP to account for uncertainty, supporting decision‐makers in balancing timely market access with the risks associated with uncertainty in the benefits of new pharmaceuticals.
Impact of myelodysplasia‐related and additional gene mutations in intensively treated patients with NPM1‐mutated AML
Authors: Cocciardi Sibylle , Saadati Maral , Weiß Nina , Späth Daniela , Kapp‐Schwoerer Silke , Schneider Isabelle , Meid Annika , Gaidzik Verena I. , Skambraks Sabrina , Fiedler Walter , Kühn Michael W. M. , Germing Ulrich , Mayer Karin T. , Lübbert Michael , Papaemmanuil Elli , Thol Felicitas , Heuser Michael , Ganser Arnold , Bullinger Lars , Benner Axel , Döhner Hartmut , Döhner Konstanze
Published: January 2025

This study aimed to evaluate the impact of the myelodysplasia‐related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with NPM1‐mutated (NPM1mut) AML. Targeted DNA sequencing of 263 genes was performed in 568 NPM1mut AML patients (median age: 59 years) entered into the prospective AMLSG 09‐09 treatment trial. Most commonly co‐mutated genes were DNMT3A (49.8%), FLT3‐TKD (25.9%), PTPN11 (24.8%), NRAS (22.7%), TET2 (21.7%), IDH2 (21.3%), IDH1 (18%), and FLT3‐ITD (17.3%). MRG mutations were identified in 18.1% of cases (18–60 years: 9.8%; >60 years: 28.7%). When focusing on the 470 patients with 2022 ELN favorable‐risk NPM1mut AML, multivariable analysis for event‐free survival (EFS) identified age (p < 0.001), DNMT3AR882 (p < 0.001), IDH1 (p = 0.007), and MRG mutations (p = 0.03) as unfavorable factors, cohesin gene co‐mutations (p = 0.001) and treatment with gemtuzumab ozogamicin (p = 0.007) as favorable factors. Restricting the analysis to a subset of CR/CRi patients with available data on NPM1mut measurable residual disease (MRD) status in blood post cycle 2 in the model, MRG mutations lost their significant effect, whereas DNMT3AR882, MYC, and cohesin gene mutations retained the adverse and favorable effects. For OS, age (p < 0.001), DNMT3AR882 (p = 0.042), IDH1 (p = 0.045), and KRAS (0.003) mutations were unfavorable factors, sole favorable factor was IDH2 co‐mutation (p = 0.037). In 2022 ELN favorable‐risk NPM1mut AML, MRG mutations are associated with inferior EFS; however, this effect is no longer present when considering NPM1mut MRD status post cycle 2; DNMT3AR882 and MYC mutations remained adverse, and cohesin gene mutations favorable prognostic factors independent of the NPM1mut MRD status.
Successful Pregnancies During Crizotinib Therapy for Anaplastic Lymphoma Kinase Positive Lymphoma
Authors: Guglielmana Veronica , Fusi Francesco Maria , Giardini Valentina , Cocito Federica , Gambacorti‐Passerini Carlo
Published: January 2025

Anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma (ALCL) typically affects young individuals and, despite high responsiveness to cytotoxic drugs, relapses occur in over 50% of patients. Crizotinib has improved outcomes, but its management in patients desiring parenthood remains an issue. This study presents the first description of four successful pregnancies during crizotinib treatment for ALK+ALCL: a female patient achieving two pregnancies through assisted reproductive technologies (ART), temporarily discontinuing crizotinib and maintaining a complete remission (CR), and a male patient conceiving naturally while on continuous therapy. These cases demonstrate crizotinib potential to support conception without compromising disease control, even in the absence of specific guidelines on treatment discontinuation.
Portal‐Vein Compression Caused by Double‐Pigtail Plastic Biliary Stent
Authors: Akiyama Shinsuke , Wada Masaya , Inokuma Tetsuro
Published: January 2025

Introduction

Reports of pseudoaneurysms associated with biliary self‐expandable metallic stent (SEMS) placement have been increasing. Recently, cases of hepatic pseudoaneurysm rupture caused by double pigtail plastic stents (DPS) have also been reported. The symptoms of pseudoaneurysms are often non‐specific, and many cases are diagnosed only after rupture. Therefore, early detection and appropriate treatment are required.

Case Presentation

A 45‐year‐old woman presented with obstructive jaundice caused by pancreatic head cancer, with imaging revealing common bile duct stenosis and intrahepatic bile duct dilation. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to place a DPS in the left hepatic duct, relieving jaundice. However, follow‐up contrast‐enhanced computed tomography (CE‐CT) revealed differences in arterial‐phase blood flow between the liver lobes without reduction in portal vein blood flow. Therefore, the compression and stenosis of the left branch of the portal vein caused by the DPS were clearly identified using three‐dimensional computed tomography (3D‐CT). The DPS was replaced with a straight‐type stent, preventing further complications. The patient subsequently underwent successful pancreaticoduodenectomy without any surgical complications.

Conclusion

This is a case of portal vein compression caused by double‐pigtail plastic biliary stent. By promptly recognizing the differences in arterial‐phase blood flow between the liver lobes and replacing the DPS with a straight‐type plastic stent, complications, such as portal vein pseudoaneurysm formation, rupture, embolism, or thrombosis, were successfully avoided.
Comparative Evaluation of Three Rapid Influenza Diagnostic Tests for Detection of Influenza A and B Viruses Using RT‐PCR as Reference Method
Authors: Yin Hailun , Wu Wenjuan , Lv Yuyang , Kou Hanlin , Sun Yuzhen
Published: January 2025

To evaluate the performance of three rapid influenza diagnostic tests (RIDTs) for detecting influenza A and B viruses compared to RT‐PCR. A total of 291 subjects with acute respiratory infections were enrolled. Respiratory specimens were collected and tested for influenza A and B viruses using three RIDTs. The results were compared with those obtained using an RT‐PCR assay from Shanghai Berger Medical Technology Co. Ltd. as the reference method. Among the 291 subjects, 119 (40.9%) tested positive for influenza A virus and 38 (13.1%) for influenza B virus by RT‐PCR. The sensitivities of the three RIDTs for influenza A virus were 92.4%, 89.1%, and 79.8%, respectively, while their specificities were 98.8%, 98.8%, and 100%, respectively. For influenza B virus, the sensitivities of the three RIDTs were 92.1%, 92.1%, and 73.7%, respectively, and their specificities were 100%, 100%, and 100%, respectively. The positive predictive values (PPVs) for influenza A virus were 98.2%, 98.1%, and 100%, respectively, while the negative predictive values (NPVs) were 94.5%, 92.4%, and 86.9%, respectively. For influenza B virus, the PPVs were all 100%, and the NPVs were 99.2%, 99.2%, and 97.7%, respectively. The three evaluated RIDTs demonstrated high specificity but varied sensitivity for detecting influenza A and B viruses. Negative results from RIDTs should be confirmed by RT‐PCR, especially during peak influenza seasons. The high PPVs suggest that positive RIDT results are reliable for influenza diagnosis, while the high NPVs indicate that negative results are more likely to be true negatives.
A record of monsoon rainforest variability from the Kimberley region in northwestern Australia
Authors: Rudd Rachel C. , Dixon Teresa , Callow John Nikolaus , Gadd Patricia S. , Maizma Sabika , Jacobsen Geraldine , Moss Patrick , McGowan Hamish
Published: January 2025

Northern Australia experiences extreme seasonality via the Indo‐Australian summer monsoon, with high inter‐annual variability in hydroclimate. Understanding the influence of hydrological variability on the landscape through the period of human occupation provides important environmental context to support the interpretation of the rich archaeological and rock art records of the region. The development of terrestrial records of environmental change has remained challenging due to the limited traditional palaeoenvironmental archives in the region. This study reports on the potential of sediments from ecologically significant monsoon rainforest patches to further elucidate the palaeoenvironmental history of the Kimberley. An ~19 000‐year record of monsoon rainforest variability is presented, inferred from pollen, charcoal and major element geochemical analysis. Monsoon rainforest‐associated taxa vary in abundance through the deglacial and the Holocene, which is compared to broad‐scale hydroclimate variability inferred from previous studies in the region. The persistence of arboreal, riparian and monsoon rainforest‐associated taxa suggest a positive moisture balance at the site throughout the period archived. Fire activity inferred from micro‐ and macrocharcoal is greatest over the last ~6000 years, and broadly corresponds to periods when monsoon rainforest‐associated taxa are less abundant. Challenges remain in using this type of site as an archive of environmental change, but they also present an opportunity to extend previous records both spatially and temporally with thousands of monsoon rainforest patches present across the Kimberley, and similar ecosystems found across northern Australia.
Cold Water Swimming and Pregnancy: A Scoping Review and Consensus Recommendations
Authors: Shawe J , Felton M , Harper JC , Harper C Mark , Stidson R , Tipton M , Blowers S , Fraser K , Hingley S , McGrath E , Bainbridge G , Heather Massey
Published: January 2025

Introduction

Cold water swimming has increased in popularity and women wish to swim throughout pregnancy. There is a lack of evidenced‐based guidance to make decisions about the safety of immersion in cold water during pregnancy.

Methods

Closed social media groups were asked for specific questions in relation to cold water swimming and pregnancy. This highlighted concerns including water temperature, risks to the mother and fetus, and water quality. To find evidence‐based answers, a series of meetings brought together clinicians and researchers with expertise in cold water physiology, exercise physiology, fertility, obstetrics, neonatology, midwifery, water epidemiology, public health and representatives from the Open Water Swimming Society and an Open Water swimming social enterprise.

Results

Published data were examined via a scoping review process and four studies and eight reports were identified. Recommendations were made with evidence graded (mostly grade 4 expert opinion).

Conclusion

Research gaps highlight the need for research to enable accurate advice to determine whether it is safe for pregnant women to swim outdoors in cold water.
Validity and Reliability of the Arabic Cough Severity Index
Authors: Alrabiah Hamad F. , Alqarni Nawaf , Alrajhi Nuha , Basfar Aban , Mesallam Tamer A. , Farahat Mohamed , Malki Khalid H.
Published: January 2025

Objectives

This study aimed to translate and validate the Cough Severity Index (CSI) into Arabic (A‐CSI) and to evaluate its validity and reliability among patients with chronic cough.

Methods

This cross‐sectional descriptive questionnaire‐based validation study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2023 and August 2024. The CSI was translated from English into Arabic using the forward‐backward method. Its reliability was assessed using Cronbach's alpha and test–retest reliability. Its construct validity was assessed using exploratory factor analysis (EFA), and its internal consistency was assessed using Cronbach's alpha. Its discriminant validity was determined using the Mann–Whitney U test, and its reproducibility was evaluated using the intraclass correlation coefficient (ICC).

Results

Data were collected from 100 participants, 50 with chronic cough and 50 healthy controls. The mean age was 41.56 ± 14.28 years in the chronic cough group and 35.48 ± 10.02 years in the healthy control group. The A‐CSI exhibited high reproducibility (ICC = 0.896) and excellent internal consistency (Cronbach's alpha = 0.966). EFA identified three factors explaining 66.41% of the variance, with all items having communalities > 0.3. The A‐CSI exhibited significant discriminant validity between the chronic cough and healthy control groups (p < 0.001).

Conclusion

The A‐CSI is a reliable and valid tool for assessing chronic cough in Arabic‐speaking patients, making it suitable for both clinical practice and research.

Level of Evidence

Level 3.
The Long‐Term Effect of Childhood Otitis Media on Speech‐in‐Noise Testing at Ages 9 and 13
Authors: Reijers Stefanie N. H. , Vroegop Jantien L. , Kremer Bernd , van der Schroeff Marc P.
Published: January 2025

Objective

To investigate the relationship between a history of otitis media (OM) in early childhood and speech reception thresholds (SRT) in later childhood, using the Dutch digits‐in‐noise (DIN) test at ages 9 and 13 years.

Methods

This study was conducted within the Generation R study, a prospective birth cohort in Rotterdam, the Netherlands. Children underwent pure‐tone audiometry and DIN testing at ages 9 (2011–2015) and 13 (2016–2020) years. Regression analyses and a linear mixed model were used to examine associations between OM history and SRT in noise, accounting for repeated measurements within individuals.

Results

At baseline (age 9 years), 2063 children were included with a mean SRT of −5.6 (SD = 2.0). At follow‐up (age 13 years), 3382 children were included with a mean SRT of −7.4 (SD = 1.4). A positive association was found between recurrent acute OM (RAOM) and DIN test outcomes, with an estimated coefficient of 0.55 (95% CI = 0.26, 0.84; t‐value = 3.70). Socioeconomic status and multilingualism did not significantly predict DIN test performance.

Conclusion

A history of RAOM may potentially influence SRT outcomes in later childhood, with higher DIN scores observed in the RAOM group. While the effect sizes between the groups are small to moderate, these findings highlight the importance of considering the potential long‐term effects of OM in both clinical practice and future research. Further studies are needed to better understand these relationships.

Level of Evidence

2 (cohort study).
Advances in moyamoya disease: pathogenesis, diagnosis, and therapeutic interventions
Authors: He Shihao , Zhou Zhenyu , Cheng Michelle Y. , Hao Xiaokuan , Chiang Terrance , Wang Yanru , Zhang Junze , Wang Xilong , Ye Xun , Wang Rong , Steinberg Gary K. , Zhao Yuanli
Published: January 2025

Moyamoya disease (MMD) is a type of cerebrovascular disease characterized by occlusion of the distal end of the internal carotid artery and the formation of collateral blood vessels. Over the past 20 years, the landscape of research on MMD has significantly transformed. In this review, we provide insights into the pathogenesis, diagnosis, and therapeutic interventions in MMD. The development of high‐throughput sequencing technology has expanded our understanding of genetic susceptibility, identifying MMD‐related genes beyond RNF213, such as ACTA2, DIAPH1, HLA, and others. The genetic susceptibility of MMD to its pathological mechanism was summarized and discussed. Based on the second‐hit theory, the influences of inflammation, immunity, and environmental factors on MMD were also appropriately summarized. Despite these advancements, revascularization surgery remains the primary treatment for MMD largely because of the lack of effective in vivo and in vitro models. In this study, 16 imaging diagnostic methods for MMD were summarized. Regarding therapeutic intervention, the influences of drugs, endovascular procedures, and revascularization surgeries on patients with MMD were discussed. Future research on the central MMD vascular abnormalities and peripheral circulating factors will provide a more comprehensive understanding of the pathogenic mechanisms of MMD.
Structural and Dynamic Assessment of Disease‐Causing Mutations for the Carnitine Transporter OCTN2
Authors: Jokiel Johannes , Bermudez Marcel
Published: January 2025

Primary carnitine deficiency (PCD) is a rare autosomal recessive genetic disorder caused by missense mutations in the SLC22A5 gene encoding the organic carnitine transporter novel type 2 (OCTN2). This study investigates the structural consequences of PCD‐causing mutations, focusing on the N32S variant. Using an alpha‐fold model, molecular dynamics simulations reveal altered interactions and dynamics suggesting potential mechanistic changes in carnitine transport. In addition, we identify mutation hotspots (R169, E452) across the SLC family with the major facilitator superfamily (MFS) fold. Our data demonstrates the applicability of structural modeling for linking genetic information and clinical observations and providing a rationale for the influence of disease‐causing mutations on protein dynamics.
Infrared Image Enhancement Based on Guided Filtering and Adaptive Algorithm and Its FPGA Implementation
Authors: Song Hongfei , Wang Ziqian , Cao Wenxiao , Zhang Yunpeng , Leng Xue
Published: January 2025

Detail enhancement and noise suppression are critical to the performance of infrared imaging systems, and a method for enhancing infrared images based on guided filters is introduced in this paper. Firstly, the guidance filter and Gaussian filter are used to decompose the original infrared image into the base layer and the detail layer, and then the adaptive histogram equalization method is used to enhance the overall brightness and contrast of the base layer. For the detail layer, we will guide the filtering to obtain the gain factor through the “” rule processing, on this basis, the detail gain function is constructed to apply to the processing of the detail layer, and finally the basic layer and the detail layer are fused to obtain the final result image. The proposed method is compared with six other infrared image enhancement algorithms under different data sets and analyzed using subjective and objective evaluation indicators. The experimental data show that the proposed method can effectively improve the overall contrast and local details of the image and has good scene adaptability. Finally, we transplanted the algorithm to the FPGA bottom layer for implementation, and for 640 512 resolution images, the final implementation effect is almost no different from that on the PC side.
A library of proton lineal energy spectra spanning the full range of clinically relevant energies
Authors: DeCunha J. M. , Missiaggia M. , Newpower M. , Traneus E. , La Tessa C. , Mohan R.
Published: January 2025

Purpose

In locations where the proton energy spectrum is broad, lineal energy spectrum‐based proton biological effects models may be more accurate than dose‐averaged linear energy transfer (LETd) based models. However, the development of microdosimetric spectrum‐based biological effects models is hampered by the extreme computational difficulty of calculating microdosimetric spectra. Given a precomputed library of lineal energy spectra for monoenergetic protons, a weighted summation can be performed which yields the lineal energy spectrum of an arbitrary polyenergetic beam. Using this approach, lineal energy spectra can be rapidly calculated on a voxel‐by‐voxel level.

Acquisition and Validation Methods

Monoenergetic proton tracks generated using Geant4‐DNA were imported into SuperTrack, a GPU‐accelerated software for calculation of microdosimetric spectra. Libraries of proton lineal energy spectra which span the energy range of 0–300 MeV were computed. The libraries were validated by comparison to Monte Carlo calculations in the literature, as well as lineal energy spectra measured experimentally with a tissue equivalent proportional counter.

Data Format and Usage Notes

The lineal energy libraries have been made available in three data formats, two are plain‐text, .csv and .les, and one binary encoded, root. Library files include the lineal energy bin abscissa in keV per micron and the unnormalized number of counts occurring within that bin. A computational technique for summation of the library files to yield the lineal energy of a polyenergetic beam is described in this work.

Potential Applications

The lineal energy libraries can be used to rapidly determine the lineal energy spectra at the location of cell cultures for in‐vitro experiments and in each voxel of a treatment plan for in‐vivo outcome modelling. These libraries have already been incorporated into RayStation 2023B‐IonPG for lineal energy spectra calculation and we anticipate they will be incorporated into further dose calculation engines and Monte Carlo toolkits.
Neuromuscular Ultrasound Training in Neuromuscular Fellowship Programs in Canada: Minding the Gap
Authors: Banerjee Ankur , Khayambashi Shahin , Jewett Gordon , Mobach Theodore , Phan Cecile , Daniels Vijay , Beecher Grayson
Published: January 2025

Introduction/Aims

Neuromuscular ultrasound (NMUS) is gaining prominence as a valuable tool for diagnosing neuromuscular disorders at the point of care. Neuromuscular disorder diagnostic criteria guidelines have begun incorporating NMUS findings. As interest grows, fellowship programs must consider incorporating training into their curricula. This study evaluated the current state of NMUS training, potential barriers, and interest in training across Canadian neuromuscular fellowship programs.

Methods

A 23‐question online survey was developed and distributed via email to all 10 neuromuscular fellowship program directors across Canada.

Results

Seven (70%) programs responded to the survey. There was general agreement among programs on the value of NMUS, however, only one (14.3%) program reported they would consider recent graduates to be competent in NMUS. Critical barriers to incorporation of NMUS training included lack of a formalized curriculum, faculty expertise and time, and equipment. Two (28.6%) programs reported that accessibility of equipment and one (14.3%) that faculty expertise was not a barrier to NMUS training. Two (28.6%) programs have local NMUS training options available to fellows (in only one program is NMUS training mandatory). All programs expressed interest in additional training opportunities, and three (43%) programs reported taking steps toward incorporating NMUS training into their curricula.

Discussion

NMUS training is in its infancy in Canada, with several common barriers identified across programs. There is universal interest in further NMUS training opportunities for fellows, highlighting the importance of a common approach to addressing the educational gap to support development of formalized NMUS training mechanisms in Canada.
Chemical Fingerprinting and Multivariate Analysis of Different Grades of Farfarae Flos Using HPLC and UPLC‐ESI‐Q/TOF‐MS/MS
Authors: Zhang Yilei , Zhu Yihan , Zhang Gang , Gao Jing , Yan Yonggang , Chen Ying , Guo Qi , Yang BingYue , Peng Liang
Published: January 2025

Introduction

Farfarae Flos is widely used as a traditional herbal medicine. Currently, its size has been the primary grading criterion used in market circulation. Whether this empirical criterion can accurately reflect the quality of the medicinal material has not been systematically studied.

Objective

This study aimed to evaluate the quality of Farfarae Flos from different regions based on their grades.

Methods

Ultra‐high performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight mass spectrometry (UPLC‐ESI‐Q/TOF‐MS/MS) were applied to study the chemical constituents of Farfarae Flos; high performance liquid chromatography (HPLC) was used to quantify the content of Farfarae Flos samples. Meanwhile, fingerprint analysis and chemometric methods, including principal component analysis (PCA) and analysis of variance (ANOVA), were used to evaluate the quality differences among 33 batches of Farfarae Flos samples of different grades.

Results

A total of 95 individual components were identified in Farfarae Flos. Fingerprint analysis revealed 23 common peaks, with fingerprint similarity among the 33 batches ranging from 0.838 to 0.995. PCA divided the 33 batches of Farfarae Flos into three categories based on their grades. ANOVA indicated significant differences in five of the 14 main active components across different grades of Farfarae Flos, with two components showing extremely significant differences. HPLC content determination showed that the content of 11 main active components was positively correlated with the grades of Farfarae Flos.

Conclusion

This method is straightforward, efficient, and reliable, offering a valuable reference for establishing quality grading standards and ensuring the quality control of Farfarae Flos.
Comparing the Introduction and Implementation of Noninvasive Prenatal Testing (NIPT) in Japan, the Netherlands, and the United States: An Integrative Review
Authors: Connor Chloe , Sato Taisuke , Bianchi Diana W. , Fenton Kathleen , Somani Elika , Turriff Amy , Berkman Benjamin , Hendriks Saskia
Published: January 2025

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in‐depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan—countries with similar economic status—to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake. We included 184 sources, including white and gray literature and non‐English sources. We identified 17 considerations that were documented to have influenced the decision whether to introduce NIPT across five domains: clinical considerations, ethical considerations and societal values, financial considerations, demand and capacity and applicable oversight. Fewer factors seem to have been considered in the US as compared to Japan or the Netherlands. Countries subsequently made choices on how to implement NIPT—we identified 35 such choices. While most of the identified choices were eventually considered by all three countries, they made different decisions (e.g., on out‐of‐pocket costs). In 2022, the estimated proportion of pregnant persons who used NIPT was 58% in the Netherlands, 49% in the US, and 9% in Japan. While differences in cultural values, population characteristics, and healthcare systems explain some variation, we identified other more adaptable aspects of the decision‐making process (e.g., oversight) that may be useful for countries introducing NIPT or similar technologies to consider.
Relationship Between Radiation Therapy and Fecal Incontinence in Patients Treated for Localized Prostate Cancer: Results of the French ICONES Study
Authors: Belkacemi Yazid , Coraggio Gabriele , Debbi Kamel , Sirmai Laura , Hollande Clemence , Rambaud Elise , Hadhri Asma , Li Xie , Hassani Wissal , Levy Michael , Vordos Dimitri , Ingels Alexandre , Loganadane Gokoulakrichenane , De La Taille Alexandre
Published: January 2025

Background

Radiation‐induced late fecal incontinence (LFI) is one of the most quality‐of‐life impairing symptoms in prostate cancer. We aimed to assess the impact of radiotherapy (RT) technique and dose‐volume effects on LFI using a robust score.

Methods

We identified 409 patients who underwent curative intent using standard fractionated radiation therapy, 190 of them were finally included and analyzed. The severity of LFI was assessed using the Jorge & Wexner score.

Results

With a median follow‐up of 55 months (range 15–96) months, LFI crude rate was 11.5%. In the multivariate analyses, image‐guided radiotherapy (IGRT), rectal maximum dose (Dmax) and anal canal minimum dose (Dmin) were significantly associated with LFI risk. The use of IGRT was associated with lower risk of LFI (p = 0.02); higher rectum Dmax (≥ 68.4 Gy; p = 0.02) and anal canal Dmin (≥ 6.4 Gy; p = 0.04) were associated with increased risk.

Conclusion

Our results suggest a significant impact of the total dose delivered to the anorectal volumes and the use of IGRT to spare organs at risk during radiation delivery.
Population exposure–response analysis of the effect of ritlecitinib on eyebrow assessment and eyelash assessment in patients with alopecia areata
Authors: Wang Yuchen , Huh Yeamin , Lejeune Alexandre
Published: January 2025

Ritlecitinib is an orally bioavailable, small molecule that has been approved by the U.S. Food and Drug Administration (FDA) as a once‐daily oral treatment option for people 12 years of age and older with severe alopecia areata. This article assessed the exposure–response (ER) relationship of eyebrow and eyelash assessment (EBA/ELA) scores on ritlecitinib and compared them to the Severity of Alopecia Tool (SALT) score (primary endpoint) ER relationship on ritlecitinib. EBA and ELA both are numeric rating scales (NRS) with four levels (0 the most severe, 3 the normal). Longitudinal ER modeling with ordinal regression was conducted to describe ritlecitinib efficacy regarding the hair regrowth in eyebrows and eyelashes separately. The average concentration in the time interval between two adjacent EBA/ELA records was used as the exposure metric. The developed models described the longitudinal EBA/ELA profile and the responder rates adequately. The ER models and the model‐based simulations implied that the tested doses in the phase IIb/III clinical trial are in the ascending region, but the magnitude of loading dose effect on earlier efficacy is different across the efficacy endpoints of EBA, ELA, and SALT scores (which could be explained by the estimated [concentration at half maximum effect]). The established longitudinal ER relationships supported the selection of 50 mg dose for overall Alopecia areata (AA) patients with impaired eyebrow and eyelash hairs. The presented analysis using the ordinal regression model can be utilized in any ER analysis where PD response is an ordinal categorical variable.
Self‐directed learning—a framework for inclusion ‘In’ and ‘Through’ Education – A systematic review
Authors: Morris Thomas Howard , Koutsouris George , Stentiford Lauren , Bremner Nicholas
Published: January 2025

There is a dearth of knowledge regarding how self‐directed learning and inclusion relate as concepts. In this paper, we explore how self‐directed learning and inclusion are discussed together in the educational literature. With the aim of advancing our conceptual and theoretical understanding in this regard, we present the findings of a systematic review that critically explores the relevant literature on self‐directed learning and inclusion. We included peer‐reviewed texts with an explicit focus on both inclusion and self‐directed learning in any educational phase. There were no restrictions on date of publication or methodology adopted. We searched five databases in July 2023: British Education Index, Education Research Complete, ERIC, International Bibliography of the Social Sciences, Australian Education Index, and Web of Science. We located 19 studies published in the past 15 years—8 studies concerned childhood education settings and 11 studies were written in the context of adult education, with the majority from higher education. We analysed the texts using thematic analysis and key findings were that: (1) self‐directed learning can be used as a framework to promote both inclusion ‘in’ education (as in pedagogical methods and strategies) and ‘through’ education (as in educational products and outcomes); and (2) engaging with self‐directed learning has the potential to further inclusion and social justice aims in education. However, these findings can only be interpreted by taking into consideration the tensions associated with inclusion that were rarely acknowledged in the included studies.

Context and implications

Rationale for this study: To date there is limited literature on how self‐directed learning and inclusion relate to each other.

Why the new findings matter: Our findings suggest that the connections between self‐directed learning and inclusion are not unproblematic, which reflects the complexities of inclusion.

Implications for teachers and researchers: Key insights gained through this process include that (1) self‐directed learning can be used as a framework to promote both inclusion ‘in’ education (as in pedagogical methods and strategies) and ‘through’ education (as in educational products and outcomes); and (2) engaging with self‐directed learning has the potential to further inclusion and social justice aims in education. However, it is essential to consider that the majority of studies reviewed in this present work were small‐scale and cross‐sectional in nature. Therefore, this field remains an important open door for further research.
Relationships among soil test potassium forms influenced by clay mineralogy
Authors: Ahlersmeyer Andrew , Clay David , Kovács Péter , Osterloh Kristopher , Rekabdarkolaee Hossein Moradi , Clark Jason
Published: January 2025

Potassium fertilizer recommendations for optimal crop production may be improved by considering the ratio between expanding 2:1 layer silicates (smectite) with non‐expanding 2:1 layer silicates (illite). However, the interactive effects between clay mineralogy and various soil tests are not well understood. This study evaluated the relationships among soil test K (STK), water‐soluble K, HNO3‐extractable K, pH, apparent cation exchange capacity (CECa), soil organic matter, clay content, and smectite:illite ratios. Soil samples (0–15 cm) were collected from 41 locations in central and eastern South Dakota, with textures ranging from sandy loam to clay. Data were partitioned into soils with smectite:illite ratios < 1 (illitic), ≥1 but ≤4.5 (smectitic), and > 4.5 (highly smectitic). Mean pH and CECa were lowest in illitic soils, higher in smectitic soils, and highest in highly smectitic soils, whereas STK and water‐soluble K were lowest in highly smectitic soils relative to illitic and smectitic. Correlation analysis also showed that STK decreased with increasing smectite:illite ratio. These results suggest that exchangeable and water‐soluble K forms are reduced when the proportion of smectite increases. There was a strong, positive relationship between STK and HNO3‐extractable K across all three smectite:illite ratio groups. For soil pH, however, the relationship with STK was positive for illitic and smectitic soil groups, but negative for highly smectitic soils. Overall, these results suggest that the smectite:illite ratio influences the relationship among soil parameters and STK. This improves our understanding of the influence of clay mineralogy on plant‐available K and the implications for K fertilizer recommendations.
After the Johannesburg II Declaration, What Next for Ecological Sustainability in BRICS? Perspectives on Green Innovations and Green Transitions
Authors: Uche Emmanuel , Okere Kingsley I. , Ngepah Nicholas
Published: January 2025

Advancing ecological sustainability, a major focus of the SDGs, necessitates evaluating the influence of green energy, sustainable technology, and resource utilization on ecological load capacity factors—an area that has remained underexplored in existing research. Also, the LCF method, which elucidates the unique features of the supply and demand dynamics in the natural environment, is still not used by BRICS environmental modelers. This study examined panel data of pertinent LCF predictors spanning from 1980 to 2021. The analysis utilized several advanced methodologies, and a new viewpoint was presented through the application of the panel‐frequency domain Granger causality test. The results demonstrate that (i) green transitions notably enhance LCF across various quantile distributions, and (ii) green technologies exert a moderately positive influence on LCF. The analysis suggests that ongoing shifts towards clean energy and the encouragement of eco‐friendly technological innovations necessitate well‐planned policies to enhance LCF within the BRICS nations.
Photoirradiation‐ and Extracellular‐Matrix‐Encouraged Photon‐Transition Switching Regulates Spatiotemporal Sequential Photoimmunotherapy
Authors: Wang Hai , Hu Feixiang , Wei Wuyang , Wu Wencheng , Yang Qiaoling , Qin Wen , Fang Chao , Dong Xiulin , Zhou Yang , Zhang Kun
Published: January 2025

As two main phototherapy means, photodynamic therapy (PDT) and photothermal therapy (PTT) have different photon‐transition avenues decided by the aggregation state of photosensitizers (PSs), and thus PDT or PTT efficiency can be regulated by regulating PSs aggregation. A co‐assembly formulation consisting of IR780 iodide PSs and pentafluorophenyl trifluoroacetate is constructed through intermolecular interactions, followed by coating with hyaluronic acid. Initially, the uniform distribution of IR780 PSs favors more reactive oxygen species birth to implement PDT when entering cells since its photon‐transition avenue through the sequential process intersystem crossing transfer–collision energy transfer is predominant. After hyaluronidase and laser irradiation‐induced structural collapse of co‐assembly, free IR780 aggregates due to hydrophobic interactions even though they are excreted out of cells, and then, these IR780 aggregates produce heat through the nonradiative relaxation process to execute PTT. Such a spatiotemporal sequential PDT–PTT phototherapy encourages antitumor immune responses and mitigates immunosuppression, thus accomplishing the spatiotemporal sequential photoimmunotherapy against breast cancer progression. Through such tumor microenvironment‐adaptable and laser‐duration‐decided aggregation state alteration, photon‐transition switching is regulated and more insights are provided into single PSs‐mediated sequential PDT–PTT and photoimmunotherapy.