bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the effect of pentoxifylline on the prevention of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study
Authors: Saleh Sondos S. , Sherif Diaa Eldin Moussa , Sabri Nagwa A. , Shawki May A.
Published: October 2024

Background

Paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients.

Results

A simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity.

Conclusion

Oral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly.

Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535.
Breeding for water-logging tolerance in pigeonpea: current status and future prospects
Authors: Belliappa Shruthi H , Bomma Naresh , Pranati Jwala , Soregaon Chandrakant D. , Hingane Anupama J. , Basavaraj P. S. , Naik S. J. Satheesh , Lohithaswa H. C. , Muniswamy S. , Mushoriwa Hapson , Kumar C. V. Sameer , Gangashetty Prakash I.
Published: October 2024

Pigeonpea is grown in semi-arid tropics where the annual precipitation ranges from 200 to 800 mm and soil orders comprising of Inceptisols, Entisols, Alfisols, Vertisols, Mixed soils, and Aridisols. During monsoons, the semi-arid tropics also receive up to 140–180 mm/day rainfall for a span of 5–10 days, highlighting the chances of waterlogging in an early vegetative stage of pigeonpea, causing 25–30% yield loss in the Indian subcontinent. Waterlogging is a state where soil reaches saturation at submergence, creating an anaerobic condition in the root zone of the plants. As a result, plant withering, leaf chlorosis, stunted growth, lowered photosynthetic rate and plant mortality is evidenced widely. In response to waterlogging, the formation of aerenchyma cells, lenticels and adventitious roots were noticed as morphological adaptations. Whereas, the production of proline, peroxidase, superoxide dismutase, ethylene and alcohol dehydrogenase (ADH) as biochemical modifications. The minimal breeding efforts for waterlogging tolerance in pigeonpea may be the reason for the susceptibility of current varieties to waterlogging stress. This review emphasized the importance of breeding for waterlogging tolerance in pigeonpea. It focused on the morphological, physiological and biochemical adaptations of a plant when subjected to waterlogging stress. It accentuated the need for a standard screening protocol for waterlogging tolerance. Breeding strategies inclusive of novel single pod descent method, marker-assisted selection and rapid generation advancement techniques are discussed in detail.
Exploring Science Identity and Latent Factors of Student Gains in a Place-based Marine Science CURE Designed to Provide Access to Hawaiʻi Students from Historically Marginalized Ethnicities
Authors: Ambrosino Christine M. , Gorospe Kelvin D. , Limeri Lisa B. , Correa-Garcia Seaenna , Rivera Malia Ana J.
Published: October 2024

An assessment of latent factors of learning gains and student reflections are used to explore the intersecting factors that impact students practicing science in an immersive, culturally-responsive CURE and describe how these factors may contribute towards building an undergraduate research experience within a Native Hawaiian Place of Learning.
Low-stakes Scientist Spotlight Assignment Demonstrates High Value and Multiple Effects for Introductory Biology Students
Authors: Rivera Angelita T. , Chong Shaelin , Kim Jerick , Owens Melinda T.
Published: October 2024

Students disproportionately mentioned Scientist Spotlights, assignments showing the personal and scientific lives of counter-stereotypical scientists, as an influential course component. They perceived multiple effects of Scientist Spotlights, including seeing diversity in science, increased self-efficacy, and seeing scientists as people.
Assessing the value of combined use of distributed acoustic sensing and multicomponent vertical seismic profiling data with network-based full-waveform inversion and uncertainty quantification: A case study in Alberta, Canada
Authors: Zhang Tianze , Cai Xiaohui , Hall Kevin , Innanen Kristopher
Published: October 2024

Distributed acoustic sensing (DAS) technology, deployed in a vertical seismic profiling (VSP) experimental configuration, has emerged as a candidate for nondisruptive and low-cost seismic monitoring of CO2 geostorage and plume evolution. As a means of extracting information from these data, full-waveform inversion (FWI) has likewise received significant attention because it uses relatively complete physical models of wave propagation and because of its sample-by-sample incorporation of data information. Recent artificial neural network-based FWI algorithms (built with, for instance, recursive neural networks [RNN]) have added to FWI a range of flexible and efficient tools for gradient computation and options for uncertainty assessment and initial model proxies. An important current research area for the use of DAS data is to better understand how they change our confidence levels in the inversion results for FWI. In particular, we seek to understand whether DAS data or conventional geophone data alone are optimal for FWI in the CO2 problem, and if not, to what degree they complement each other. The Snowflake 4D VSP data set, which includes multioffset and multiazimuth broadband sources illuminating fiber-optic cable and densely sampled accelerometer in the borehole, has been acquired by our group to directly address these questions. In this study, we quantify uncertainty by evaluating the posterior model covariance matrix from the inverse Hessian matrix at the end of RNN-FWI runs on the Snowflake baseline data, invoking a velocity-density parameterization, and involving mixtures of accelerometer and DAS data. In this uncertainty quantification context, the complementary effect of combining accelerometer and DAS data is evident in the [Formula: see text] and [Formula: see text] models. In the pursuit of reliable and low-cost monitoring tools, this supports continued consideration of a multicomponent sensors supported by DAS approach.
Guide to Understanding and Supporting International Medical Graduates in Hematology/Oncology by the ASCO International Medical Graduates Community of Practice
Authors: Dizman Nazli , Bakouny Ziad , Haykal Tarek , Riano Ivy , Desai Aakash , Butt Ayesha , Basu Arnab , Zhao Dan , Saad Eddy , Saliby Renee Maria , Gosain Rohit , Gosain Rahul , Ardeshir Fatemeh , Deng Lei , Matt-Amaral Laurie , Arnaoutakis Konstantinos , Bekaii-Saab Tanios , Manochakian Rami , Marshall Ariela , Forde Patrick , Murphy Martina , Subbiah Vivek , Chavez-MacGregor Mariana , Owonikoko Taofeek K. , Lopes Gilberto , Aggarwal Charu , Lee Alfred I. , Choueiri Toni K.
Published: October 2024

PURPOSE

International medical graduates (IMGs) are an essential component of the oncology workforce in the United States, comprising a third of all practicing oncologists and almost half of hematology/oncology fellows. In this article, we discuss the contributions of IMGs in the US oncology workforce, review unique challenges faced by IMGs, and propose potential solutions to overcome these challenges.

METHODS

ASCO's IMG Community of Practice was established with the mission to connect, mentor, guide, raise awareness, and overcome the challenges unique to IMGs interested in pursuing medical oncology in the United States. The content of this article is based on discussions at the IMG Community of Practice meetings at ASCO's 2023 and 2024 Annual Meetings.

RESULTS

IMGs bring an inherent diversity of thought and experience to the oncology workforce. They provide high-quality, culture- and language-concordant care to a diverse population of patients with cancer. However, IMGs in oncology face significant hardships throughout their careers, including visa-related restrictions, psychosocial and cultural struggles, as well as differential treatment while applying for residency and fellowship training, and early career positions. Greater awareness of these challenges among the members of the hematology/oncology community, along with institutional and individual efforts to support IMGs, is warranted.

CONCLUSION

We encourage oncology professionals and institutions to join our efforts in recognizing the unique paths of IMGs and providing support and advocacy to maximize the potential of IMGs in the US oncology workforce.
Effects of carbon nanotubes on the isotropic to nematic phase transition in nematic liquid crystal elastomer
Authors: Mukherjee Prabir K.
Published: October 2024

The isotropic to nematic phase transition on nematic liquid crystal elastomer - carbon nanotubes composites has been studied theoretically. The model free energy density has been constructed using Flory Huggins theory of isotropic mixing and Landau-de Gennes theory. The effects of carbon nanotubes and external mechanical stress on the isotropic to nematic phase transition of the nematic liquid crystal elastomer-carbon nanotubes composites have been discussed. The volume fraction of carbon nanotubes dependence of the isotropic to nematic transition temperature, mechanical strain and strain birefringence has been calculated. The weak first-order character of the isotropic to nematic phase transition on nematic liquid crystal elastomer-carbon nanotubes composites has been predicted.
Nodule-Specific NRF2-Targeted Upregulation in Patients With KEAP1 Mutations and Familial Nontoxic Multinodular Goiter
Authors: Nishihara Eijun , Fukata Shuji , Hirokawa Mitsuyoshi , Higuchi Miyoko , Ito Mitsuru , Nishikawa Mitsushige , Miyauchi Akira , Matsuse Michiko , Mitsutake Norisato , Ito Yuka , Hishinuma Akira , Kogai Takahiko , Akamizu Takashi
Published: October 2024

Context

Kelch-like ECH-associated protein 1 (KEAP1) is associated with nuclear factor erythroid-2–related factor 2 (NRF2) and promotes NRF2 degradation in normal conditions. Genetic abnormality in KEAP1 is a rare disease and presents with familial multinodular goiter.

Objective

This study assessed the clinical and molecular findings concerning nodular formation in the thyroid gland of patients harboring KEAP1 germline mutations.

Methods

Next-generation sequencing analysis targeting goiter-associated genes was performed on 39 patients with familial multinodular goiter. The expression of NRF2-targeted genes from surgical thyroid specimens of patients with KEAP1 mutations were analyzed using a whole-transcript expression array and immunohistochemistry.

Results

We found 5 probands with pathogenic heterozygous mutations in KEAP1 (p.Q86*, p.L136P, p.V411fs, p.R415C, and p.R483H) that had no meaningful concomitance with mutations of other goiter-associated genes at germline and somatic levels. Their common histopathological features showed multinodular goiters in the entire thyroid gland with few degenerative lesions or complications of malignancy and slow proliferation indicating less than 1% at the Ki-67 labeling index. Among 42 NRF2-targeted genes, antioxidant genes were most frequently upregulated (11/12) in the nodule, followed by detoxification genes (6/11). Immunohistochemical analysis showed relatively high expression of glutathione peroxidase 2 and NAD(P)H quinone oxidoreductase 1 (representative NRF2-targeted genes) in the nodules of various patients harboring KEAP1 mutations.

Conclusion

KEAP1 germline heterozygous mutations exert excessive NRF2 activity in the thyroid gland and may confer cytoprotective effects even under abundant reactive oxygen species associated with thyroid hormone production, resulting in thyroid hyperplasia with scarce degradation.
Alterations and Clinical Value of Peripheral Lymphocyte Subsets and Inflammatory Factors in Paragangliomas
Authors: Zhou Yue , Zhang Wenqian , Cui Yunying , Li Tianyi , Wang Yu , Li Ming , Tong Anli
Published: October 2024

Objectives

Given the pivotal role of immune and inflammatory responses in tumor patients, the present study aimed to explore alterations and the clinical value of peripheral lymphocyte subsets and inflammatory factors in pheochromocytomas/paragangliomas (PPGLs).

Methods

The clinical data of 327 patients, including 102 patients with metastatic PPGLs, were retrospectively analyzed. Peripheral lymphocyte subsets were determined by flow cytometry. Relationships between immune and inflammatory parameters and clinicopathological characteristics were evaluated by intergroup comparisons and correlation analyses. Univariate and multivariate logistic regression analyses were employed to identify metastatic indicators. The corresponding nomogram was constructed and evaluated for discrimination and calibration.

Results

The median age at diagnosis was 45.0 years, and duration of follow-up was 3.0 years. Compared with those in younger patients (< 45.0 years), most lymphocyte subsets were significantly reduced in older patients (≥ 45 years) (P < .05). The count of lymphocytes, CD3+ T cells and CD4+ T cells were negatively correlated with 24-hour urinary epinephrine and plasma metanephrine levels (R = −0.2 ∼ 0.1, P < .05). In addition, patients with lymph node (n = 37) or bone metastases (n = 41) had a lower percentage of CD4+ T cells (P < .05). Multivariate analysis revealed that CD3+ T cell count ≥ 1446.50/μL, CD4+ T cell% < 39.95%, CD8+ T cell% < 24.95%, CD4+/CD8+ T cell ratio < 2.88, B cell% ≥ 8.65%, TNF-alpha < 12.45 pg/mL, IL-8 < 30.50 pg/mL, and platelets ≥ 269.50 × 109/L were significant indicators of metastatic PPGLs. The area under the curve (AUC) of the nomogram was 0.800 (95% CI: 0.736-0.865).

Conclusion

Immunosenescence, characterized by immune dysfunction with aging, was observed in PPGLs. Higher epinephrine and metanephrine levels might impair host immune response. Monitoring changes in peripheral lymphocyte subsets and serum cytokines could indicate patients’ conditions, especially the occurrence of metastasis.
Associations of Serum Testosterone and SHBG With Incident Fractures in Middle-aged to Older Men
Authors: Grahnemo Louise , Marriott Ross J , Murray Kevin , Tyack Lauren T , Nethander Maria , Matsumoto Alvin M , Orwoll Eric S , Vanderschueren Dirk , Yeap Bu B , Ohlsson Claes
Published: October 2024

Context

As men age, circulating testosterone (T) decreases, circulating SHBG increases, and the risk of fracture increases. It is unclear if circulating T, independently of comorbidities, is associated with fracture risk in men.

Objectives

To determine associations for T and SHBG with incident fractures in men.

Methods

We utilized the large (n = 205 973 participants, 11 088 any fracture cases, 1680 hip fracture cases, 1366 forearm fracture cases) and well-characterized UK Biobank cohort. Associations were modeled using Cox regressions, adjusting for multiple comorbidities/covariates, imputing for missing information, and assessing nonlinearity using cubic splines.

Results

For T, not considering SHBG, there was a nonlinear association with hip but not forearm fractures, with the lowest risk in the second quintile. However, in models adjusted for SHBG or using calculated free T, lower T was associated with a higher risk for fractures at all evaluated bone sites. Lower SHBG was strongly associated with a lower risk of hip and forearm fractures (Q1 vs Q5, hip 0.55, 0.47-0.65; forearm 0.62, 0.52-0.74).

Conclusion

Low circulating SHBG is strongly associated with a low risk of fracture at all evaluated bone sites, while the associations of circulating T with fracture risk are of lesser magnitude, nonlinear, inconsistent among fracture site, and affected by adjustment for SHBG. These findings demonstrate that circulating SHBG, rather than T, is a major independent biomarker of fracture risk in men. Consequently, both total T and SHBG should be assessed when examining the relationship of endogenous T concentrations with fractures in middle-aged to older men.
Jill Johnston in Motion
Authors: Croft Clare
Published: October 2024

Performer, activist, and writer Jill Johnston was a major queer presence in the history of dance and 1970s feminism. She was the first critic to identify postmodernism’s arrival in American dance and was a fierce advocate for the importance of lesbians within feminism. In Jill Johnston in Motion, Clare Croft tracks Johnston’s entwined innovations and contributions to dance and art criticism and activism. She examines Johnston’s journalism and criticism—in particular her Village Voice columns published between 1960 and 1980—and her books of memoir and biography. At the same time, Croft attends to Johnston’s appearances as both dancer and audience member and her physical and often spectacular participation at feminist protests. By bringing together Johnston’s criticism and activism, her writing and her physicality, Croft emphasizes the effect that the arts, particularly dance, had on Johnston’s feminist thinking in the 1970s and traces lesbian feminism’s roots in avant-garde art practice.
Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice
Authors: Xie Xuefeng , Li Jianshuang , Zhang Xue , Mo Shaomei , Li Ang , Sun Tian-Yi , Xie Feng-Yun , Luo Shi-Ming , Wang Guang , Ou Xiang-Hong , Sun Qing-Yuan , Zhou Qinghua
Published: October 2024

Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog−/−) mice. Our findings revealed that Endog−/− mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog−/− and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog−/− and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.
Hepatocyte differentiation requires anisotropic expansion of bile canaliculi
Authors: Bebelman Maarten P. , Belicova Lenka , Gralinska Elzbieta , Jumel Tobias , Lahree Aparajita , Sommer Sarah , Shevchenko Andrej , Zatsepin Timofei , Kalaidzidis Yannis , Vingron Martin , Zerial Marino
Published: October 2024

During liver development, bipotential progenitor cells called hepatoblasts differentiate into hepatocytes or cholangiocytes. Hepatocyte differentiation is uniquely associated with multi-axial polarity, enabling the anisotropic expansion of apical lumina between adjacent cells and formation of a three-dimensional network of bile canaliculi. Cholangiocytes, the cells forming the bile ducts, exhibit the vectorial polarity characteristic of epithelial cells. Whether cell polarization feeds back on the gene regulatory pathways governing hepatoblast differentiation is unknown. Here, we used primary mouse hepatoblasts to investigate the contribution of anisotropic apical expansion to hepatocyte differentiation. Silencing of the small GTPase Rab35 caused isotropic lumen expansion and formation of multicellular cysts with the vectorial polarity of cholangiocytes. Gene expression profiling revealed that these cells express reduced levels of hepatocyte markers and upregulate genes associated with cholangiocyte identity. Timecourse RNA sequencing demonstrated that loss of lumen anisotropy precedes these transcriptional changes. Independent alterations in apical lumen morphology induced either by modulation of the subapical actomyosin cortex or by increased intraluminal pressure caused similar transcriptional changes. These findings suggest that cell polarity and lumen morphogenesis feed back to hepatoblast-to-hepatocyte differentiation.
Jag1 represses Notch activation in lateral supporting cells and inhibits an outer hair cell fate in the medial cochlea
Authors: de Haan Sandra , Corbat Agustin A. , Cederroth Christopher R. , Autrum Lisa G. , Hankeova Simona , Driver Elizabeth C. , Canlon Barbara , Kelley Matthew W. , Andersson Emma R.
Published: October 2024

Notch signaling patterns the cochlear organ of Corti, and individuals with the JAG1/NOTCH2-related genetic disorder Alagille syndrome can thus experience hearing loss. We investigated the function of Jag1 in cochlear patterning and signaling using Jag1Ndr/Ndr mice, which are a model of Alagille syndrome. Jag1Ndr/Ndr mice exhibited expected vestibular and auditory deficits, a dose-dependent increase in ectopic inner hair cells, and a reduction in outer hair cells. Single cell RNA sequencing of the organ of Corti demonstrated a global dysregulation of genes associated with inner ear development and deafness. Analysis of individual cell types further revealed that Jag1 represses Notch activation in lateral supporting cells and demonstrated a function for Jag1 in gene regulation and development of outer hair cells. Surprisingly, ectopic ‘outer hair cell-like’ cells were present in the medial compartment and pillar cell region of Jag1Ndr/Ndr cochleae, yet they exhibited location-dependent expression of the inner hair cell fate-determinant Tbx2, suggesting Jag1 is required for Tbx2 to drive inner hair cell commitment. This study thus identifies new roles for Jag1 in supporting cells, and in outer hair cell specification and positioning.
The implementation of an automated method for solution term-tracking as a basis for symbolic computational dynamics
Authors: Forehand D I M , Cartmell M P
Published: October 2024

This article proposes that additional mathematical information, inherent and implicit within mathematical models of physical dynamic systems, can be extracted and visualized in a physically meaningful and useful manner as an adjunct to standard analytical modelling and solution. A conceptual methodology is given for a process of term-tracking within ordinary differential equation (ODE) models and solutions for engineering dynamics problems, and for a visualization based on a powerful new Mathematica implementation of the standard Tooltip graphical user interface facility. It is shown that the method is logical, generic, and unambiguous in its application, and that a useful visualization tool can be devised, and structured in such a way that the user can be given as much or as little information as is required to assimilate the problem to hand. The article shows by means of examples of code written expressly for the purpose that a term-tracking and visualization methodology can be constructed in a computationally effective manner within Mathematica and applied to a semi-automated variant of the method of multiple scales. It is implicitly obvious that this approach can therefore be applied to almost any algorithmic symbolic solution method, and therefore there could be physical applications which are potentially well beyond the chosen domain of non-linear engineering dynamics.
Assessing the Risk of Postoperative Delirium Through Comprehensive Geriatric Assessment and Eastern Cooperative Oncology Group Performance Status of Elderly Patients With Gastric Cancer
Authors: Itami Takefumi , Yamamoto Kazuyoshi , Kurokawa Yukinori , Saito Takuro , Takahashi Tsuyoshi , Momose Kota , Yamashita Kotaro , Tanaka Koji , Makino Tomoki , Yasunobe Yukiko , Akasaka Hiroshi , Fujimoto Taku , Yamamoto Koichi , Nakajima Kiyokazu , Eguchi Hidetoshi , Doki Yuichiro
Published: October 2024

Background

Postoperative delirium is especially common and often problematic among elderly patients undergoing surgery. This study aimed to explore factors that can predict postoperative delirium in elderly patients undergoing gastric cancer surgery.

Methods

This cohort study included 255 patients age 75 years or older who underwent gastric cancer surgery between July 2010 and December 2020. All the patients underwent preoperative comprehensive geriatric assessment (CGA) evaluation by a geriatrician. In addition to the CGA items, this study investigated the association between postoperative delirium and clinicopathologic factors, including Eastern Cooperative Oncology Group performance status (ECOG-PS).

Results

The most common postoperative complication was delirium, present in 31 patients (12.2%). The group with delirium was significantly more likely to have ECOG-PS ≥ 2, diabetes mellitus, cardiovascular disease, or cerebral infarction. The CGA showed frailty in the Instrumental Activities of Daily Living scale (IADL), the Mini-Mental State Examination (MMSE), the Vitality Index (VI), and the Geriatric Depression Scale 15 (GDS-15). In the multivariate analysis, the independent risk factors for delirium were ECOG-PS ≥ 2 (P = 0.002) and MMSE-frailty (P < 0.001). Using an MMSE score of ≤ 23 and an ECOG-PS score of ≥ 2 as cutoffs, postoperative delirium was predicted with a sensitivity of 80.7% and a specificity of 74.1%.

Conclusion

Postoperative delirium might be more easily predicted based on the combination of MMSE and ECOG-PS for elderly patients with gastric cancer undergoing gastrectomy.
Pain Medication Data from the 2021 and 2022 National Football League Prescription Drug Monitoring Program
Authors: Hill Kevin P. , Kroenke Kurt , Wasserman Erin B. , Mack Christina , Ling Geoffrey S.F. , Mayer Thom , Solomon Gary S. , Sills Allen
Published: October 2024

We report 2021 and 2022 prescription drug monitoring program data that include pain medication prescriptions, including over-the-counter medications, issued to NFL players by either club physicians or external medical providers and entered in the NFL electronic medical record. Of 3142 players who signed a contract with at least one NFL Club during the 2021 season, there were 14,903 prescriptions for pain medications issued to 2207 players. During the 2022 season, there were 14,880 prescription pain medications issued to 2189 players (out of a population of 3152). Notably, most pain medication prescriptions across the two seasons were for nonsteroidal anti-inflammatory agents (NSAIDs; 85.1%), whereas only 2.9% were for opioids. Despite the demanding physical nature of professional football and the need for pain management during a season, the prevalence of opioid prescriptions among NFL players appears to be similar to and, in some cases, potentially lower than previous U.S. population-based data.
Upskilling India: The national policy on skill development and entrepreneurship
Authors: Shaikh Shena , Ganesh M. P
Published: October 2024

Background India’s National Policy for Skill Development and Entrepreneurship (NPSDE) was designed to capture the demographic dividend and upskill India’s youth, creating an ‘Athmanirbhar Bharat’ (self-reliant India) and in the process, also drive economic growth. Policy and Implications The NPSDE’s dual focus on skill development and entrepreneurship was intended to create a framework for empowering India’s workforce and fostering a culture of innovation. However, the policy has encountered several issues, including the ineffective functioning of Sector Skill Councils (SSCs), inadequate infrastructure, and insufficiently skilled trainers. Additionally, the policy’s efforts to include marginalized groups, particularly women, have fallen short due to entrenched social barriers and gender biases, impacting the effectiveness of training programs. Recommendations To improve the effectiveness of the NPSDE, we propose the following recommendations -adopt an entrepreneurial ecosystem approach to enhance coordination and support within the skill development framework; explicitly define ‘skill’ and ‘skilling’ to better align with socio-political realities and address barriers faced by marginalized individuals; and design training initiatives with an empowerment perspective, focusing on access to resources, agency, and social change. We feel these steps can help direct the NPSDE to create a more inclusive and impactful skilling environment. Conclusions While the NPSDE represents a significant effort towards upskilling India and fostering self-reliance and entrepreneurship, its implementation has revealed critical limitations. The policy’s progress has been insufficient, with persistent issues in meeting industry needs and addressing socio-economic barriers. Future revisions of the policy should focus on systemic improvements, adopting a more inclusive approach to skilling, and addressing the socio-political dimensions of skill valuation to better support India’s developmental aspirations.
Standardised and Objective Dietary Intake Assessment Tool (SODIAT): Protocol of a dual-site dietary intervention study to integrate dietary assessment methods
Authors: Bobokhidze Eka , Weech Michelle , Petropoulou Katerina , Wilson Thomas , Pugh Jennifer , Fallaize Rosalind , Garcia-Perez Isabel , P.-W. Lo Frank , R Solis Adrian , Vickar Juliet , Giannarou Stamatia , Mylonas George , Lo Benny , Lloyd Amanda J , Koulman Albert , Beckmann Manfred , Draper John , Frost Gary , Lovegrove Julie A
Published: October 2024

Introduction Current dietary assessment methods face challenges in accurately capturing individuals’ dietary habits, undermining the efficacy of public health strategies. The ‘Standardised and Objective Dietary Intake Assessment Tool’ (SODIAT)-1 study aims to assess the effectiveness of three emerging technologies (urine and capillary blood biomarkers, and wearable camera technology) and two online self-reporting dietary assessment tools to monitor dietary intake. Methods This randomised controlled crossover trial will recruit 30 participants (aged 18-70 years and BMI of 20-30 kg/m2) from Imperial College London and the University of Reading. Exclusion criteria include recent weight change, food allergies/intolerances, following restrictive diets, certain health conditions and medication use. Interested volunteers will be directed to an online screening questionnaire via REDCap and eligible participants will attend a pre-study visit. Volunteers will consume, in a random order, two highly-controlled diets (compliant and non-compliant with UK guidelines) for four days each. Each study arm will be separated by at least one-week. During each test period, dietary intake will be monitored continuously using wearable cameras and self-recorded using eNutri (food frequency questionnaire) and Intake24 (24-hour dietary recall). Urine and capillary blood samples will be collected for biomarker analysis. Data analysis will assess the accuracy of dietary reporting across these methods using Lin’s concordance correlation coefficient. Discussion and ethical considerations This study introduces a novel approach to dietary assessment, addressing the limitations of traditional methods by reducing misreporting and enhancing inclusivity, particularly for underrepresented populations with literacy or language barriers. However, challenges persist, such as variability in biomarker data due to failure to adhere to sample storage requirements and the practicalities of continuously wearing cameras. To protect privacy, participants will be instructed to remove cameras at inappropriate times, and artificial intelligence will be used to blur all images captured apart from food.
Effect of Methocarbamol on acute low back pain: A systematic review
Authors: Wided Bahria , Yasmine Makhlouf , Intissar Boussaid , Yasmine Walha , Elhouda Nouira Nour , Ahmed Laater
Published: October 2024

Introduction Pharamcological treatment for acute low back pain (ALBP) typically involves opioid drugs, and non-steroidal anti-inflammatory drugs (NSAIDs). Methocarbamol is utilized primarily for managing muscle spasms and pain. This systematic review aims to provide an updated synthesis of published literature on the effects of Methocarbamol on pain outcomes in ALBP. Methods This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Original articles published until December 2023 were sourced from PubMed, Embase, and the Cochrane Library. Articles focusing on the impact of Methocarbamol on pain outcomes in ALBP patients were included. Results Three studies met the inclusion criteria, published between 2018 and 2023. The total study population comprised 405 ALBP patients, with 163 receiving Methocarbamol. Compared to patients not receiving Methocarbamol, those in the Methocarbamol group showed pain improvement at one week. However, at 30 and 60 minutes after intravenous administration, Methocarbamol was less effective than Diazepam. The primary reported adverse event was nausea. Conclusion When administered in combination with Indomethacin or Naproxen, Methocarbamol shows potential for improving pain outcomes at one week in ALBP patients. However, its efficacy appears inferior to Diazepam in the short-term management of pain
A computational biology approach for the identification of potential SARS-CoV-2 main protease inhibitors from natural essential oil compounds.
Authors: Hasib Rizone Al , Ali Md. Chayan , Rahman Md. Shahedur , Rahman Md. Mafizur , Ahmed Fee Faysal , Mashud Md. Abdullah Al , Islam Md. Azizul , Jamal Mohammad Abu Hena Mostofa
Published: October 2024

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fomented a climate of fear worldwide due to its rapidly spreading nature, and high mortality rate. The World Health Organization (WHO) declared it as a global pandemic on 11th March, 2020. Many endeavors have been made to find appropriate medications to restrain the SARS CoV-2 infection from spreading but there is no specific antiviral therapy to date. However, a computer-aided drug design approach can be an alternative to identify probable drug candidates within a short time. SARS-CoV-2 main protease is a proven drug target, and it plays a pivotal role in viral replication and transcription. Methods: In this study, we identified a total of 114 essential oil compounds as a feasible anti-SARS-CoV-2 agent from several online reservoirs. These compounds were screened by incorporating ADMET profiling, molecular docking, and 50 ns of molecular dynamics simulation to identify potential drug candidates against the SARS-CoV-2 main protease. The crystallized SARS-CoV-2 main protease structure was collected from the RCSB PDB database (PDB ID 6LU7). Results: According to the results of the ADMET study, none of the compounds have any side effects that could reduce their druglikeness or pharmacokinetic properties. Out of 114 compounds, we selected bisabololoxide B, eremanthin, and leptospermone as our top drug candidates based on their higher binding affinity scores, and strong interaction with the Cys 145-His 41 catalytic dyad. Finally, the molecular dynamics simulation was implemented to evaluate the structural stability of the ligand-receptor complex. MD simulations disclosed that all the hits showed conformational stability compared to the positive control α-ketoamide. Conclusions: Our study showed that the top three hits might work as potential anti-SARS-CoV-2 agents, which can pave the way for discovering new drugs, but for experimental validation, they will require more in vivo trials.
Improving pre-exposure prophylaxis service delivery to gay men and other men who have sex with men in South Africa: Generating novel insights with a nudgeathon
Authors: Long Lawrence , Chetty-Makkan Candice , Bokolo Simamkele , Govathson Caroline , Maughan-Brown Brendan , Mistri Preethi , Pascoe Sophie , Buttenheim Alison
Published: October 2024

“Indlela - Behavioural Insights for Health” a behavioural science unit focused on improving health services in South Africa developed a pragmatic behavioural design framework called N-U-D-G-E. We used the nudgeathon approach to combine our technical expertise with stakeholder knowledge to apply this framework and rapidly co-create behavioural solutions designed to improve PrEP uptake and persistence amongst gay men and other men who have sex with men (MSM) in South Africa. Over two days we took 26 stakeholders divided into five teams through the framework and identified 602 solutions which were prioritized into two ideas per team and then pitched to an expert panel. This approach uncovered several high-potential, novel light-touch solutions to some of the challenges hindering PrEP delivery to gay men and other MSM in South Africa. This format is an effective way to engage stakeholders, including policy makers, in the process of both identifying behavioural barriers to optimal health decision making as well as creating novel solutions that can be tested.
The emerging role of a Stroke Clinical Nurse Specialist (CNS) in Early Supported Discharged: Developing a pathway for stroke nursing for secondary prevention in the community. A scoping review protocol.
Authors: Byrne Sarah-Jane , Williams David J. , Patton Declan , Murphy Paul J. , Horgan Frances
Published: October 2024

Background Stroke represents a major source of mortality and morbidity globally. The role of a stroke Clinical Nurse Specialist (CNS) as an expert team member in early supported discharge (ESD) for stroke, is not well defined or described although it is well established in other models of after-hospital and out-reach specialist care in the community. A greater focus has been on patients receiving rehabilitation post-stroke, however there is a need for a more holistic approach to care which clinical nurse specialists can offer to patients as part of ESD. Nurses are often the cohesive point of contact for other after-hospital services, managing many aspects of secondary prevention. Objective The aim of this scoping review is to explore the evidence in relation to the role of the stroke nurse providing secondary prevention interventions to stroke patients in a community setting. Methods We will conduct a scoping review in accordance with the Arksey and O’Malley, 2005 1 scoping review framework and the PRISMA-ScR guidelines to map available literature on the role of the stroke nurse in post-stroke care of patients in the community. The Cochrane Central Register of Controlled Trials and Systematic literature searches including databases MEDLINE, EMBASE, CINAHL, google scholar and grey literature will be searched using keyword searches. Data will be charted and synthesised and a narrative synthesis will be conducted. Conclusions This scoping review will be used to identify gaps in the current literature and identify areas for future research in the role of the stroke nurse in ESD in relation to secondary prevention for stroke patients and inform the development of a pathway for stroke nursing in ESD.
COVID-19 and (ir)responsible (im)mobility: Reading counter-practices through Levinas and Derrida
Authors: Puggioni Raffaela
Published: October 2024

The COVID-19 pandemic has affected virtually all daily activities, relations and practices. People were expected to act responsibly by following social distancing, masking, sanitation and stay-home rules. The prevailing ethos of the time was that to protect others, one must first protect oneself. By examining the creative modalities through which (a few) people in Paris circumvented mobility restrictions to help and support those in need, this article investigates the relation between (im)mobility and (ir)responsibility. Is mobility, during a time of forced immobility, an irresponsible act? What does it mean to act responsibly during a life-threatening emergency? Does responsibility always require complete and unequivocal compliance with extant norms, or should responsibility also be evaluated in light of the motives that inspire (unauthorised) mobility? The issue of (ir)responsible (im)mobility is scrutinised here by drawing upon the work of Emmanuel Levinas and Jacques Derrida. While the former furthers our understanding of ethical relations, the latter makes us rethink the concept of response-ability and, in particular, the aporia this concept entails. As Derrida highlights, truly ethical acts are impossible for the very reason that all ethical acts are, at the very same time, responsible towards some and irresponsible towards others.
The genome sequence of the Red-legged Robberfly, Dioctria rufipes (Scopoli, 1763)
Authors: Crowley Liam M. , Sivell Olga , Sivell Duncan , Mitchell Ryan , Newell Robert ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2024

We present a genome assembly from an individual Dioctria rufipes (the Red-legged robberfly; Arthropoda; Insecta; Diptera; Asilidae). The genome sequence has a total length of 1,451.60 megabases. Most of the assembly is scaffolded into 6 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 17.69 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,218 protein-coding genes.
Allocation of Procurement Costs under the Conditions of Using the Deferral Strategy in Supply Chains
Authors: Mironov V. , Abramova E.
Published: October 2024

The article discusses the method of distributing procurement costs in the context of using the deferral strategy in the CP, which allows participants to obtain additional competitive advantages by reducing the time period from product development and raw material procurement to actual sales.

The proposed approach is based on the application of graph theory to procurement cost management, namely, the use of graph coloring algorithms for distributing or combining such costs over different time periods.

The examples discussed in the article are especially relevant in the context of turbulent modern markets, which have a direct impact on the diversity and specificity of economic relations between CP participants.
Project Change Canvas
Authors: Ferreira Raquel , Varajão João , Rodrigues Luis Silva , Sousa Rui Dinis
Published: October 2024

Project management plays a critical role in boosting the success of organizations' projects. However, no matter how well a project is managed, changes are inevitable during its execution. It is crucial to evaluate the impact of these changes before implementing them to ensure they do not compromise the project's success. Existing techniques for assessing the effects of changes have several limitations—particularly in their failure to account for how changes might affect various aspects of project management, such as scope, cost, time, resources, communication, risk, procurement, or overall success. To overcome this limitation, this article introduces a new technique – the Project Change Canvas – that enables the systematic assessment of changes in information systems and technology projects by identifying and weighing their potential impacts across all relevant project management knowledge areas.
Respiratory alkalosis as an adverse effect of safinamide?
Authors: Freitas Flávia , Rosa Beatriz , Pinto Silva Catarina , Marques Cristina , Mota João , Lemos Costa Carla , Oliveira Carlos
Published: October 2024

Respiratory alkalosis is associated with central nervous system (CNS) diseases, drugs, lung diseases and others. Safinamide is a recent anti-parkinsonian drug with anti-dyskinetic properties and a good adjunct to L-dopa therapy during the activation period, with no significant adverse effects described. The authors present a case of a 71-year-old woman, with Parkinson’s disease treated with levodopa/benserazide, safinamide, amitriptyline, sertraline and diazepam. She made multiple visits to the emergency department due to progressive dyspnoea and asthenia, with primary respiratory alkalosis, which was thought to be caused by anxiety-induced hyperventilation and treated accordingly. After a comprehensive study, it was determined that the most probable cause of the respiratory alkalosis was pharmacological. There was a clinical and temporal agreement with the introduction of safinamide.
Co-infection of cytomegalovirus and Leishmania without splenomegaly resulting in immunosuppression in an HIV-negative patient
Authors: Bhatia Inder Preet Singh , Tripathi Siddharth , Singh Amulyajit , Hasvi Jayaraj , Rajan Amit , Tukaram Dahake Vandana
Published: October 2024

Background: Leishmaniasis is caused by the parasite Leishmania donovani and transmitted by the bite of the sand fly vector Phlebotomus. This disease is endemic in the Bihar region of India. There are three common forms of the disease – cutaneous, mucosal and visceral leishmaniasis. The most common presentation of this disease is prolonged unexplained fever with hepatosplenomegaly. Case description: We report an unusual case of pyrexia of unknown origin (PUO) in a patient who was extensively worked up for PUO. She was found to have low CD4 counts even though serial samples were negative for HIV. Workup for PUO revealed a positive result for cytomegalovirus (CMV) IgM and polymerase chain reaction (PCR), fundoscopy suggestive of CMV retinitis and bone marrow biopsy suggestive of visceral leishmaniasis. Interestingly, there was no evidence of hepatosplenomegaly. She was diagnosed as a case of CMV infection and visceral leishmaniasis resulting in immunosuppression and was managed with parenteral ganciclovir followed by oral valganciclovir and amphotericin respectively. She had a dramatic response to the treatment and was discharged after two months of in hospital management. Conclusion: Co-infection of CMV and Leishmania in an immunocompromised patient with HIV-negative status without hepatosplenomegaly posed a diagnostic dilemma and is a rare presentation. This report shows the importance of diagnosis of this co-infectious state, which upon management with ganciclovir and amphotericin lead to resolution of symptoms and pancytopenia. Clinicians should be aware of the unusual presentation to avoid missing the diagnosis of this potentially life-threatening treatable condition.
Sustainability in NHS planning and development
Authors: Cox Sarah
Published: October 2024

Sarah Cox explores some of the strategies being trialled and implemented by NHS services around the UK to reduce the impact of healthcare on the environment, highlighting the need to continue striving for the target of net zero by 2040.
Repurposed drugs
Authors: Winter George
Published: October 2024

In this month's article, George Winter discusses the potential for repurposed drugs to change the therapeutic landscape