bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Group Dynamics in Pharmaceutical Education: An Examination of Instructor- Led Team Formation Methods
Authors: Shimomura Yuki , Utsumi Miho
Published: May 2024

Background: Problem-based learning (PBL) has evolved as a prominent educational approach in medical and pharmaceutical education, shifting from traditional knowledge-intensive methods to a learner-centered model. It emphasizes the development of problem-solving skills and self-learning abilities. However, despite the effectiveness of PBL, challenges such as free riding in group settings have been identified, impacting group dynamics and overall learning outcomes. Therefore, this study aimed to determine the influence of grouping methods on student behavior and how it influences the presence of free riders and active learners within the educational setting. It also aimed to elucidate the distinctive characteristics and attributes that differentiate free riders from active learners, thus providing a comprehensive understanding of the dynamics in pharmaceutical education.
Methods:
The study involved 255 second-year students from Kobe Gakuin University, randomly assigned to three groups: motivation (formed on career aspirations), grade point average (GPA; academic performance), and randomized groups. Students engaged in PBL activities, including case presentations, problem definition, brainstorming, formulation of learning objectives, self-study, and synthesis of new information. After PBL class, students answered questionnaires. Data collection included demographic information, self and peer evaluations, and qualitative comments. Students were categorized as "free riders," "active learners," or "general learners" based on their peer evaluation scores.
Results: Teams formed based on GPA were more prone to free riding behavior, while motivation-based teams exhibited a higher level of active participation. Additionally, active learners generally had higher GPAs and positive self-evaluations compared to free riders.
Conclusion: Motivation-based teams could effectively enhance active learning and reduce the incidence of free riders in PBL settings. In contrast, grouping students solely based on GPA may promote passive learning behaviors. These findings suggest that instructors should consider students’ interests when forming teams for PBL in pharmaceutical education. Such an approach could foster a more engaging and productive learning environment, potentially improving educational outcomes.
Identification and validation of drugs for repurposing in Glioblastoma: a computational and experimental workflow
Authors: Gonzalez Nazareno , Küper Melanie Pérez , Fallit Matías Garcia , Agudelo Jorge A. Peña , Candia Alejandro J. Nicola , Velandia Maicol Suarez , Videla-Richardson Guillermo A. , Candolfi Marianela
Published: May 2024

Purpose
Glioblastoma (GBM) remains a formidable challenge in oncology due to its invasiveness and resistance to treatment, i.e. surgery, radiotherapy, and chemotherapy with temozolomide. This study aimed to develop and validate an integrated model to predict the sensitivity of GBM to alternative chemotherapeutics and to identify novel candidate drugs and combinations for the treatment of GBM.
Methods
We utilized the drug sensitivity response data of 272 compounds from CancerRxTissue, a validated predictive model, to identify drugs with therapeutic potential for GBM. Using the IC50, we selected 'potentially effective' drugs among those predicted to be blood-brain barrier permeable via in silico algorithms. We ultimately selected drugs with targets overexpressed and associated with worse prognosis in GBM for experimental in vitro validation.
Results
The workflow proposed predicted that GBM is more sensitive to Etoposide and Cisplatin, in comparison with Temozolomide, effects that were validated in vitro in a set of GBM cellular models. Using this workflow, we identified a set of 5 novel drugs to which GBM would exhibit high sensitivity and selected Daporinad, a blood-brain barrier permeant NAMPT inhibitor, for further preclinical in vitro evaluation, which aligned with the in silico prediction.
Conclusion
Our results suggest that this workflow could be useful to select potentially effective drugs and combinations for GBM, according to the molecular characteristics of the tumor. This comprehensive workflow, which integrates computational prowess with experimental validation, could constitute a simple tool for identifying and validating compounds with potential for drug repurposing in GBM and other tumors.
Development of 3D scaffolds models using parameterized modeling
Authors: Bié Gabriel de Souza Vieira , Silveira Zilda de Castro , Aroca Rafael Vidal , Branciforti Marcia Cristina
Published: May 2024

Tissue engineering is a technique for regenerating living tissue using portions of the patient's own tissue, which are dissociated into cells and cultured on biological or synthetic supports before being transferred to the patient. In this context, the present work seeks to develop implant models (scaffolds) for the replacement of trabecular bone tissue, in accordance with requirements like porosity and interconnected pores. All design development was aimed at the manufacturing of scaffolds using material extrusion process. For the development of this work, the Grasshopper program was utilized, an extension of Rhino that facilitates the creation of structures easily modifiable by parameters. The model developed involves applying the Voronoi 2D diagram in two perpendicular planes to generate extruded structures along a vector perpendicular to the plane of the respective diagram. This approach aims to create a pore structure interconnected in two directions. Prototypes have been produced that fulfill most of the properties required by a scaffold. In addition, the geometry of the prototypes was very close to the original model, even using low resolution 3D printers.
A cluster randomized controlled trial to assess the impact of the ‘Caring for Providers to Improve Patient Experience’ intervention on person-centered maternity care in Kenya and Ghana: Study Protocol
Authors: Afulani Patience A. , Getahun Monica , Ongeri Linnet , Aborigo Raymond , Kinyua Joyceline , Ogolla Beryl A. , Okiring Jaffer , Moro Ali , Oluoch Iscar , Dalaba Maxwell , Odiase Osamuedeme , Nutor Jerry , Mendes Wendy Berry , Walker Dilys , Neilands Torsten B.
Published: May 2024

Background
Poor person-centered maternal care (PCMC) contributes to high maternal mortality and morbidity, directly and indirectly, through lack of, delayed, inadequate, unnecessary, or harmful care. While evidence on poor PCMC prevalence, as well as inequities, expanded in the last decade, there is still a significant gap in evidence-based interventions to address PCMC. We describe the protocol for a trial to test the effectiveness of the “Caring for Providers to Improve Patient Experience” (CPIPE) intervention, which includes five strategies for provider behavior change, targeting provider stress and bias as intermediate factors to improve PCMC and to address inequities.
Methods
The trial will assess the effect of CPIPE on PCMC, as well as on intermediate and distal outcomes, using a two-arm cluster randomized controlled trial in 40 health facilities in Migori and Homa Bay Counties in Kenya and Upper East and Northeast Regions in Ghana. Twenty facilities in each country will be randomized to 10 intervention and 10 control sites. The primary intervention targets are all healthcare workers who provide maternal health services. The intervention impact will also be assessed first among providers, and then among women who give birth in health facilities. The primary outcome is PCMC measured with the PCMC scale, via multiple cross-sectional surveys of mothers who gave birth in the preceding 12 weeks in study facilities at baseline (prior to the intervention), midline (6 months after intervention start), and endline (12 months post-baseline) (N = 2000 across both countries at each time point). Additionally, 400 providers in the study facilities across both countries will be followed longitudinally at baseline, midline, and endline, to assess intermediate outcomes. The trial incorporates a mixed-methods design; survey data alongside in-depth interviews (IDIs) with healthcare facility leaders, providers, and mothers to qualitatively explore factors influencing the outcomes. Finally, we will collect process and cost data to assess intervention fidelity and cost-effectiveness.
Discussion
This trial will be the first to rigorously assess an intervention to improve PCMC that addresses both provider stress and bias and will advance the evidence base for interventions to improve PCMC and contribute to equity in maternal and neonatal health.
Low levels of PTH predict early mortality in incident patients on hemodialysis: results from a large cohort
Authors: Aquino Hugo B.S. , Canziani Maria Eugenia F. , Barra Ana Beatriz L. , Roque-da-Silva Ana Paula , Strogoff-de-Matos Jorge Paulo , Dalboni Maria Aparecida , Moyses Rosa M.A. , Elias Rosilene M
Published: May 2024

Purpose: Parathyroid hormone (PTH) is merit as a risk factor for mortality in patients with chronic kidney disease starting dialysis in a U-shape. Most studies, however, do not focus on incident patients and those who died within the first 90 days of therapy. We evaluated PTH as a risk factor for mortality in a large cohort population in Brazil.
Methods: This is an observational cohort study that included 4,317 adult patients who initiated hemodialysis between July 1st, 2012, and June 30, 2017. The main outcome was all-cause mortality. Fine-gray sub-distribution hazard models were used to evaluate survival in the presence of a competing event (kidney transplant).
Results: median PTH levels of 252 (118, 479) pg/mL. There were 331 deaths during the first 90 days of therapy (6.7%), 430 in a 1-year follow-up (10.7%) and 1,282 (32%) during the 5-year study period. Deaths according to PTH < 150, 150-600 and > 600 pg/mL corresponded to 38.1%, 33.0% and 28.5%, respectively (p <0.001). In an adjusted model, patients who started dialysis with PTH < 150 pg/mL had a higher mortality risk within the first 90 days, but not in 1 year and 5 years after starting dialysis. Analyses in a subset of patients with a repeated PTH in 1 year (N=1,954) showed that although persistent PTH low levels (<150 pg/mL) at 1 year were significantly associated with all-cause mortality this result was not sustained after multiple adjustments.
Conclusion: PTH <150 pg/mL confers a high mortality risk in the first 90 days of dialysis. If this result reflects poor nutritional conditions deserves further investigation.
Feed-feces-fertilizer: Greenhouse study and interviews with fertilizer producers indicate persistence and negative effect of glyphosate residue in manure-based fertilizers
Authors: Birge Traci , Saloniemi Irma , Saikkonen Kari , Helander Marjo
Published: May 2024

BACKGROUND: The herbicide glyphosate is the most widely used active ingredient in pesticides globally. Residues have been found in people, livestock, food and animal feed, and in the environment, but little is known about glyphosate residue in manure-based fertilizer. “Feed-feces-fertilizer” describes how manure fertilizer can be contaminated with glyphosate. This exposure can harm sensitive plants, such as tomato, and pose a risk to effective waste disposal and nutrient cycling along principles of the circular economy. We review the use and history and present a mixed methods research based on a real-world case from Finland where glyphosate residue in poultry manure fertilizer was suspected of inhibiting commercial organic tomato production. To test the fertilizer, we grew 72 ‘Encore’ variety tomatoes for 14 weeks using the same commercial greenhouse methods. To ascertain awareness and potential contamination mitigation measures, we also contacted five fertilizer companies with sales of biogenic fertilizer in Finland, representatives of two farming organizations, and two government organizations working on nutrient cycling and agricultural circular economy.
RESULTS: The total harvest of tomatoes grown with fertilizer with glyphosate residue was 35% smaller and the yield of first-class tomatoes 37% lower than that of the control. Two of the five fertilizer companies identified poultry manure as a source of glyphosate contamination. Companies with awareness of pesticide residues reported interest in establishing parameters for pesticide residues.
CONCLUSIONS: The extent of glyphosate contamination of recycled fertilizers is unknown, but this study shows that such contamination occurs with negative impacts on crop production. The example from Finland shows that a model of co-production between fertilizer producers and state regulatory agencies to establish safe limits can benefit both fertilizer producers and their customers.
PD1 inhibitors combined with chemotherapy versus re-irradiation /chemoradiotherapy for unresectable locally recurrent T3-4 nasopharyngeal carcinoma: a retrospective study
Authors: Liu Tongxin , Sun Quanquan , Hua Yonghong , Tao Changjuan , Jiang Feng
Published: May 2024

Background
The aim of this study was to evaluate the efficacy, toxicity, and long-term outcomes of PD1 inhibitors plus chemotherapy versus re-irradiation/chemoradiotherapy in patients with unresectable locally recurrent T3-4 nasopharyngeal carcinoma (NPC).
Methods
A retrospective analysis was conducted on 42 patients with recurrent nasopharyngeal cancer (NPC) after receiving immunochemotherapy or reradiation between February 2018 and May 2022. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were determined using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression.
Results
With a median follow-up duration of 28.7 months (ranging from 7.2 to 63.9 months), the 3-year OS rate was 23.3% in the re-irradiotherapy (RI) group (N = 24) and 59.6% in the immunochemotherapy (IC) group (N = 18) (p = 0.042). The 3-year PFS, LRFS, and DMFS rates were not significantly different between the two groups (PFS: 45.3% vs. 62.6%, P = 0.482; LRFS: 54.4% vs. 62.6%, P = 0.891; DMFS: 89.8% vs. 100.0%, P = 0.489). The univariate analysis revealed that regimen (HR: 0.354, 95% CI: 0.130–0.962, P = 0.042) was significantly correlated with OS. Multivariate analysis also showed that treatment regimen (HR: 0.329, 95% CI: 0.12–0.970, P = 0.044) was the only significant prognostic factor associated with OS. The most common late toxicities in the RI group were xerostomia, deafness, and nasopharyngeal necrosis. Of these, nasopharyngeal necrosis was present in 16 patients (66.7%) and in 10 patients (41.7%) at a grade 3 or above. Nasopharyngeal necrosis is the main cause of death in the RI group. In contrast, in the IC group, grade 3 or higher immune-related adverse events or late adverse events were not observed.
Conclusion
For unresectable locally recurrent NPC, re-irradiation is an effective treatment; nevertheless, the survival obtains are usually surpassed by serious late complications. For these individuals, chemotherapy in addition to an anti-PD-1 checkpoint inhibitor may be a helpful course of treatment.
A Novel Model Based on Cnn–vit Fusion and Ensemble Learning for Automatic Detection of Pes Planus
Authors: SELÇUK Turab , Yılmaz Abdurrahman
Published: May 2024

Pes planus, commonly known as flatfoot, is a condition in which the medial arch of the foot is abnormally low or absent, leading to the inner part of the foot having less curvature than normal. With the availability of large datasets, deep neural networks have shown promising capabilities in recognizing foot structures and accurately identifying pes planus. In this study, we developed a novel fusion model by combining the Vgg16 convolutional neural network (CNN) model with the vision transformer ViT-B/16 to enhance the detection of pes planus. This fusion model leverages the strengths of both CNN and ViT architectures, resulting in improved performance compared to reports in the literature. Additionally, ensemble learning techniques were employed to ensure the robustness of the model. Through 10-fold cross-validation, the model demonstrated high sensitivity, specificity, and F1 score values of 97.4%, 96.4%, and 96.8%, respectively. These results highlight the effectiveness of the proposed model in quickly and accurately diagnosing pes planus, making it suitable for deployment in clinics or healthcare centers. By facilitating early diagnosis, the model can contribute to better management of treatment processes, ultimately leading to improved quality of life for patients.
Coronary heart disease with pulmonary embolism: a case report
Authors: Xu Junqing , Jiang Mengxin , Wang Feng , Yang Kaiqiang , Xu Yingjiang , Wang Yujiu , Dong Shengjun
Published: May 2024

Background: Coronary heart disease and pulmonary embolism are both thrombotic diseases, and now, patients with coronary heart disease and pulmonary embolism are not uncommon in clinical practice. However, there are some challenges in clinical diagnosis of pulmonary embolism due to their overlapping primary symptoms such as chest tightness and dyspnea. This confluence frequently leads to underdiagnosis or misdiagnosis of pulmonary embolism, thus precipitating treatment delays and compromising patient outcomes. Here we reported a patient who successfully diagnosed with both diseases and ultimately underwent coronary artery bypass grafting, anticoagulant and antiplatelet drug therapy, with a good prognosis.
Case presentation: A 51-year-old male with a history of hypertension for 2 years, came to local hospital due to paroxysmal chest tightness for 1 day and was diagnosed with coronary heart disease, but he refused hospitalizationour. Then, he came to our hospital for treatment due to recurring symptoms. After admission, a comprehensive examination found that D-dimer was elevated, and further computer tomography pulmonary angiography was performed to confirm the diagnosis of pulmonary embolism. This patient finally successfully received coronary artery bypass grafting with anticoagulant and antiplatelet drugs, whose prognosis is good.
Conclusions: This case has guiding significance for the treatment of patients with coronary heart disease combined with pulmonary embolism. Coronary artery bypass grafting combined with anticiagulation and antiplatelet therapy is feasible for such patients. Clinically, when diagnosing coronary heart disease, D-dimer screening should be performed, and if PE is suspected, computer tomography pulmonary angiography should be performed as soon as possible to confirm the diagnosis to decide personalized treatment strategy.
Regional lymph node changes on breast MRI in patients with early-stage breast cancer receiving neoadjuvant chemo-immunotherapy
Authors: Jacob Saya , Christofferson Anika , Fisch Samantha , Norwood Peter , Castillo Paolo , Yu Hongmei , Hirst Gillian , Soliman Hatem , Nanda Rita , Mukhtar Rita A. , Ewing Cheryl , Majure Melanie , Melisko Michelle , Rugo Hope S. , Esserman Laura , Price Elissa , Chien A. Jo
Published: May 2024

Purpose
Establishing breast MRI imaging patterns associated with neoadjuvant immunotherapy is needed to monitor response. We analyzed serial breast MRIs in patients receiving neoadjuvant chemo-immunotherapy on the ISPY-2 clinical trial.
Methods
Patients had stage 2–3 HER2-negative breast cancer in a single institution. Regimens included: weekly paclitaxel (control), weekly paclitaxel in combination with pembrolizumab, or weekly paclitaxel in combination with pembrolizumab and intra-tumoral injection of SD-101, a TLR9 agonist. All patients then received AC and underwent surgery. Regional lymph nodes were retrospectively evaluated on breast MRI at baseline, 3 wks, 12 wks and 20 wks by a single blinded radiologist. MRIs were assessed for development of new regional lymphadenopathy, or increase in longest diameter or cortical thickness of largest regional lymph node.
Results
Between 12/2015-4/2021, a total of 43 patients enrolled to the control (n = 16) and paclitaxel + pembrolizumab +/- SD-101 (n = 27) arms. 25 patients had hormone-receptor positive disease and 18 patients had triple negative disease. 12 of 27 patients (44.4%) receiving chemo-immunotherapy experienced increased lymphadenopathy within the first 12 weeks compared to 1 of 16 patients (6.3%) in the control group (p = 0.014). Increased lymphadenopathy was observed despite concomitant decrease in breast tumor size at all time points. 11 of 12 patients with increased lymphadenopathy had pathologically negative nodes at surgery. There was no association between lymphadenopathy and lower residual cancer burden (p = 0.696) or immune-related toxicity.
Conclusions
Chemo-immunotherapy was associated with early increases in regional lymphadenopathy despite decreased breast tumor size. Increased lymphadenopathy was not associated with node-positive disease at surgery.
Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model
Authors: Aragón-Navas Alba , Rodrigo Maria Jesus , Munuera Ines , Garcia-Herranz David , Subias Manuel , Villacampa Pilar , García-Feijóo Julián , Pablo Luis , Garcia-Martin Elena , Herrero-Vanrell Rocío , Bravo-Osuna Irene
Published: May 2024

This work focused on the co-encapsulation and simultaneous co-delivery of three different neuroprotective drugs in PLGA (poly(lactic-co-glycolic acid) microspheres for the treatment of glaucoma. For formulation optimization, dexamethasone (anti-inflammatory) and ursodeoxycholic acid (anti-apoptotic) were co-loaded by the solid-in-oil-in-water emulsion solvent extraction-evaporation technique as a first step. The incorporation of a water-soluble co-solvent (ethanol) and different amounts of dexamethasone resulted critical for the encapsulation of the neuroprotective agents and their initial release. The optimized formulation was obtained with 60 mg of dexamethasone and using an 80:20 dichloromethane:ethanol ratio. In the second step in the microencapsulation process, the incorporation of the glial cell line-derived neurotrophic factor (GDNF) was performed. The final prototype showed encapsulation efficiencies for each component above 50% with suitable properties for long-term application for at least 3 months. Physicochemical studies were performed by SEM, TEM, DSC, XRD, and gas chromatography. The evaluation of the kinetic release by the Gallagher-Corrigan analysis with Gorrasi correction helped to understand the influence of the co-microencapsulation on the delivery of the different actives from the optimized formulation. The final prototype was tested in a chronic glaucoma animal model. Rats received two intravitreal injections of the neuroprotective treatment within a 24-week follow-up study. The proposed formulation improved retinal ganglion cell (RGC) functionality examined by electroretinography. Also, it was able to maintain a neuroretinal thickness similar to that of healthy animals scanned by in vivo optical coherence tomography, and a higher RGC count on histology compared to glaucomatous animals at the end of the study.
Enhancing Breast Cancer Neoadjuvant Therapy Prediction with Proximity Analysis of CD8 + T Cells and Immune Landscape Integration
Authors: Liang Hongling , Huang Jianqing , Li Hongsheng , He Weixing , Ao Xiang , Xie Zhi , Chen Yu , Lv Zhiyi , zhang Leyao , Zhong Yanghua , Tan Xiaojun , Han Guodong , Zhou Jie , Qiu Ni , Jiang Ming , Xia Haoming , Zhan Yongtao , Jiao Lei , Ma Jie , Radisky Derek , Huang Jia , Zhang Xuchao
Published: May 2024

Background: In breast cancer, the spatial relationship between immune and tumor cells is increasingly recognized as critical in determining the efficacy of neoadjuvant therapy (NAT). This study investigated how the distribution of immune cells, particularly CD8+ T cells, relative to tumor cells affects treatment outcomes.
Methods: Biopsies from 104 breast cancer patients were examined, both pre- and post-NAT, using multiplex immunohistochemistry (mIHC). This study focused on the density and distribution of CD8+ T cells, CD68+ macrophages, FoxP3+ regulatory T cells, and other immune markers.
Results: The spatial proximity of CD8+ T cells within 20 µm of cancer cells (N20-CD8+T) was strongly correlated with improved clinical outcomes across diverse tumor subtypes and NAT regimens. A significant post-NAT decrease in CD4+, CD68+, and FoxP3+ cells highlights notable shifts in the tumor immune landscape. A noteworthy finding was the positive correlation between CXCL9 expression and N20-CD8+T cells, suggesting a mechanism for immune cell recruitment and interaction within the tumor microenvironment. These results highlight the complex interplay among NAT, immune cell modifications, and patient outcomes.
Conclusions: This study revealed that the proximity of N20-CD8+ T cells to tumor cells is consistently associated with favorable NAT outcomes, transcending tumor subtypes, and treatment differences. This highlights the potential of immune cell dynamics, especially CD8+ T cells, as predictive biomarkers for therapeutic responses in breast cancer, underscoring their vital role in tumor immunity.
Significance of neutrophil-to-lymphocyte ratio in predicting the efficacy of anamorelin treatment for cancer cachexia
Authors: Nakazawa Yusuke , Watanabe Kanako , Gannichida Ako , Uwagawa Tadashi , Kawakubo Takashi
Published: May 2024

Purpose: Cancer cachexia is a multifactorial syndrome characterized by persistent loss of skeletal muscle mass, adversely affecting chemotherapy tolerability and life expectancy. Despite the expected therapeutic effect of anamorelin’s appetite-promotion,its efficacy has not been investigated in clinical practice. Given the involvement of cancer-inducing cytokines in cancer cachexia, we investigated whether the inflammatory biomarker neutrophil-to-lymphocyte ratio (NLR) could predict treatment outcomes.
Methods: This study included patients receiving anamorelin for cancer cachexia associated with pancreatic, nonsmall-cell lung, gastric, and colorectal cancers between April 2021 and December 2023. Patients were classified based on their NLR (<5 or ≥5) at 4 weeks postanamorelin administration. The NLR changes before and 4 weeks after of anamorelin therapy and 1-year overall survival (OS) rates were compared between the two groups.
Results: Out of 66 patients who received anamorelin, those with NLR <5 (n = 50) at 4 weeks postanamorelin administration showed a significant decrease in mean NLR from 3.71 ± 3.12 to 2.44 ± 1.23. Conversely, patients with an NLR ≥5 at 4 weeks (n = 16) had a significant increase from 5.70 ± 2.78 to 9.52 ± 4.85. The 1-year OS was significantly increased in patients with NLR of <5. Receiver–operating characteristic (ROC) analysis suggested that an NLR <4.4 before treatment potentially change to NLR <5 after anamorelin treatment, indicating NLR’s potential as a prognostic marker.
Conclusion: NLR was suggested to be an effective indicator for predicting the therapeutic effect of anamorelin.
Genetic ancestry and male founder effects explain differences in height and lactose tolerance in 60 Caucasian populations
Authors: Grasgruber Pavel
Published: May 2024

This study aimed to examine geographical associations of genetic factors (24 Y haplogroups, 10 autosomal ancestry components) with mean male height and the occurrence of lactose tolerance-associated alleles in a sample of 60 genetically interconnected Caucasian populations of Europe, the Near East, and North Africa. The results show that Y haplogroups or their combinations often match almost perfectly the geographical occurrence of a particular autosomal ancestry (correlation coefficients reaching up to r = 0.99), demonstrating that male founder effects played a crucial role in shaping population history. Male height adjusted for major environmental factors is positively related mainly to ancestry components BHG (Baltic hunter-gatherers), Villabruna, and Yamnaya, and the combined frequency of five Y haplogroups (I1, I2a-P37.2, N, Q, R1b-U106). The frequency of the European lactose tolerance-associated allele 13910*T correlates primarily with Yamnaya ancestry and with the combination of six Y haplogroups (I1, I2a-M223, Q, R1a, R1b-S116, R1b-U106), whereas the Near Eastern allele 13915*G is predicted by Natufian ancestry and three Y haplogroups typical of Arab populations (E1b-M123, J1, T). Of further note is the fact that country-level relationships between body height and ancestry components show both concordance and stark differences with genetic studies using individual-level relationships, which can potentially have important implications. In summary, many of the findings achieved are extremely impressive and their causality can often be inferred from already documented findings. Others offer hypotheses that could be tested with more sophisticated research.
Oscillating Spatiotemporal Patterns of COVID-19 in the United States
Authors: Jalal Hawre , Lee Kyueun , Burke Donald
Published: May 2024

COVID-19 case rates in the USA wax and wane in wave-like patterns over time, but the spatial patterns of these temporal epidemic waves have not been well characterized. By analyzing state- and county-level COVID-19 case rate data for spatiotemporal decomposition modes and oscillatory patterns, we demonstrate that the transmission dynamics of COVID-19 feature recurrent spatiotemporal patterns. In addition to the well-recognized national level annual mid-winter surges, we demonstrate a prominent but previously unrecognized six-month north-south oscillation in the eastern USA (Eastern US COVID Oscillator – EUCO) that gives rise to regional sub-epidemics and travelling epidemic waves. We also demonstrate a second less prominent pattern that oscillates east-west in the northern USA (Northern US COVID Oscillator – NUCO). The drivers of these newly recognized oscillatory epidemic patterns remain to be elucidated. Since the first documented case of SARS-CoV-2 in the USA in January of 2020, the virus has caused nearly 100 million reported infections and more than 1 million deaths.1 COVID-19 incidences have waxed and waned several times a year, with month-to-month variations in intensity in different regions of the country.1 The spatiotemporal granularity of available COVID-19 data in the USA provides an unprecedented opportunity to investigate detailed epidemiological dynamics of an infectious disease. In this study, we examine this spatiotemporal data in the USA to reveal patterns that can aid in the understanding COVID-19 waves and their oscillatory behavior in the United States.
Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease
Authors: León-Lara Ximena , Pérez-Blanco Uriel , Yamazaki-Nakashimada Marco A , Bustamante-Ogando Juan Carlos , Aguilar-Gómez Nancy , Cristerna-Tarrasa Hernán , Staines-Boone Aidé Tamara , Saucedo-Ramírez Omar J , Fregoso-Zuñiga Eunice , Macías-Robles Ana Paola , Canseco-Raymundo María R , Venancio-Hernández Marco , Moctezuma-Trejo Cristina , Gámez-González Berenise , Zarate-Hernández Carmen , Ramírez-Rivera Roselia , Scheffler-Mendoza Selma , Jiménez-Polvo Nancy , Hernández-Nieto Leticia , Carmona-Vargas Jocelyn , García-Cruz María L , Zavaleta-Martínez Óscar , Román-Montes Carla M , Cervantes-Parra Victoria , González-Reynoso Anelena , Guzmán-Cotaya Rogelio , Espinosa-Rosales Francisco , Saltigeral-Simental Patricia , Espinosa-Padilla Sara , Galicia Lizbeth Blancas
Published: May 2024

Purpose.
Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette–Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD.
Methods.
Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease.
Results.
A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants.
Conclusions.
This report highlights the importance of considering TB in endemic areas and BCG in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
Prognostic value of natural killer cells in colorectal carcinomas
Authors: Helal Imen , Aissi Wafa , Abdallah Khouloud Ben , Cherif Mouna , Khanchel Fatma , Laamari Hajer , Sabbah Mariem , Brahim Ehsen Ben , Jouini Raja , Debbiche Aschraf Chadly
Published: May 2024

Backgrounds:
Although natural killer cells are considered valuable prognostic factors in several solid tumors, their role in colorectal carcinomas remains obscure. Thus, we aimed to determine the prognostic value of NK cells in colorectal carcinomas.
Methods:
We reviewed patients who were diagnosed with stage I to IV colorectal carcinomas and who underwent curative resection of the tumor. We first determined and marked the areas with the most important lymphocyte infiltration in the center and the invasive margin of the tumor. Subsequently, we identified natural killer cells by performing an immune histochemical study with a anti-CD56 antibody via the tissue microarray technique. Afterwards, we manually counted the marked cells. Multivariate analysis was performed to determine the independent prognostic factors for death.
Results:
Our study included 104 patients. The mean age was 61.6 ± 1.4 years. The median numbers of natural killer cells in the tumor center and in the invasive margin were 1/punch and 0/punch respectively. The median total number of natural killer cells/tumor was 2. The total number of natural killer cells was ≥ 2 in 49 (47.1%) tumors. No significant difference was found in the survival curves between the group of tumors with Natural Killer cells ≥ 2 and that with Natural Killer cells < 2 (p = 0.117). According to multivariate analysis, a low immunoscore and the histological subtype of mucinous adenocarcinomas were found to be independent prognostic factors associated with poor overall survival.
Conclusion:
There are few natural killer cells in tumor tissue. They have no prognostic impact on the overall survival of patients with colorectal carcinomas.
Trial registration:
The Habib Thameur Hospital Ethics Committee HTHEC-2023-23 (retrospectively registered)
Switching Behavior and Changes in Smoking Behavior by Menthol Cigarette Preference and Menthol Heated Tobacco Product Use Among Adults Who Smoke Cigarettes: An Actual Use Study
Authors: Karelitz Joshua , He Yisha , Becker Elizabeth , Vansickel Andrea
Published: May 2024

Background: Heated tobacco products (HTPs) deliver nicotine with significantly lower toxicant exposure relative to combustible cigarettes. HTPs may serve as viable tobacco harm reduction options for adults who smoke (AS) but are not able or willing to stop consuming nicotine-containing products. There is limited information on switching away from or reducing combusted cigarette consumption among AS provided with HTPs, and none assessing differences due to menthol cigarette preference or menthol HTP use.
Methods: In a six-week actual use study of HTP, AS ages 21-64 (n=615) who were not planning to quit smoking combusted cigarettes were offered free choice of HTPs (one non-menthol and two menthol varieties) to use ad libitum. Preference for smoking menthol or non-menthol cigarettes was assessed upon study entry (374 menthol; 241 non-menthol). The number of HTP sticks and combusted cigarettes consumed were measured daily. Complete switching was defined as reporting consuming zero combusted cigarettes while continuing to use the HTP research product in Week 6.
Results: Overall, 247 participants completely switched to HTP, corresponding to 21.1% of all those enrolled at baseline (n=1173) or 40.2% of the analytic sample (n=615). Among the analytic sample, we observed greater switching among AS who preferred menthol versus non-menthol cigarettes (46.8% vs 29.9%). Probability of switching increased with greater proportional use of menthol versus non-menthol HTPs. Non-menthol cigarette-preferring AS had greater increases in switching when using proportionally more menthol than non-menthol HTPs; switching remained consistently high among menthol-preferring AS. Among participants who did not switch and continued smoking at Week 6, preference for menthol cigarettes and use of proportionally greater menthol versus non-menthol HTPs were each associated with greater reductions in cigarette consumption.
Conclusions: HTP use facilitated switching away from or reducing consumption of combusted cigarettes among AS, especially when using menthol HTPs. Most AS used menthol HTPs, regardless of their incoming preference for smoking menthol or non-menthol cigarettes. Availability of HTPs in menthol and non-menthol varieties offers an increased tobacco harm reduction opportunity over non-menthol only by providing AS with smoke-free alternatives that they find appealing, reduce toxicant exposure, and can effectively support their transition away from combusted cigarettes.
Prioritizing disease-related rare variants by integrating gene expression data
Authors: Guo Hanmin , Urban Alexander Eckehart , Wong Wing Hung
Published: May 2024

Rare variants, comprising a vast majority of human genetic variations, are likely to have more deleterious impact on human diseases compared to common variants. Here we present carrier statistic, a statistical framework to prioritize disease-related rare variants by integrating gene expression data. By quantifying the impact of rare variants on gene expression, carrier statistic can prioritize those rare variants that have large functional consequence in the diseased patients. Through simulation studies and analyzing real multi-omics dataset, we demonstrated that carrier statistic is applicable in studies with limited sample size (a few hundreds) and achieves substantially higher sensitivity than existing rare variants association methods. Application to Alzheimer's disease reveals 16 rare variants within 15 genes with extreme carrier statistics. We also found strong excess of rare variants among the top prioritized genes in diseased patients compared to that in healthy individuals. The carrier statistic method can be applied to various rare variant types and is adaptable to other omics data modalities, offering a powerful tool for investigating the molecular mechanisms underlying complex diseases.
Ethnobotany of traditional plant cosmetics utilized by women; A study in Northern Ghana
Authors: Ameade Evans Paul Kwame , Aparku Josephine , Adom Emmanuel
Published: May 2024

Background
Plants with cosmetic properties have been often abandoned in research as they mostly focus on plants with medicinal value or properties and their use as food. The study therefore assessed the use of plants for cosmetic purposes among female residents in Tamale metropolis the in the Northern Region of Ghana.
Method
A cross-sectional study was thus conducted among women in the Tamale metropolis to specifically identify plants used as cosmetics and determine the level of usage among women. A convenience sampling method was used in selecting the 383 participants from 20 randomly selected communities in Tamale. A semi-structured questionnaire-guided interview was used to collect the data which was then analyzed using Microsoft Excel version 2310 and IBM Statistical Package for Social Sciences (SPSS) software version 25.0. The results of the data analysis were presented in tables and graphs. Also, multivariate analysis was used to determine the association between some variables. Statistical significance is assumed at p < 0.05 at a confidence level of 95%.
Results
A total of 19 plants belonging to 18 families were listed by women in Tamale to be used for cosmetic purposes. Out of the 383 respondents, 228 use plants for cosmetic purposes. The most preferred application areas were skin, hair and private parts whereas the main cosmetic uses were skin smoothening (33.4%), skin protection (8.1%), hair growth (13.3%), treatment of acne (11.7%), body odour (9.9%) and vaginal hygiene (5.7%). Employment status (p-value = 0.325), level of education (p – value = 0.709), the origin of growth (p-value = 0.455) and type of accommodation (p – value = 0.925) which measured the economic status of the women had no association with their usage of plants for cosmetic purposes. Marital status however had a significant association with plant cosmetic usage (p – value = 0.020).
Conclusion:
Shea butter (Vitellaria paradoxa) was the most used plant by females for smoothening the skin and enhancing hair growth. This study provided an understanding of the abandoned areas of plants concerning their cosmetic values. Continuous research is encouraged to record and preserve this indigenous knowledge.
Neural correlates of resilience under different operational definitions: A resting-state fMRI study
Authors: Tai Alan P. L. , Leung Mei-Kei , Yuen Kevin C. P. , Geng Xiujuan , Lau Way K. W.
Published: May 2024

Different operationalizations of psychological resilience, the ability to rebound from adversity, have been adopted in the literature, each representing a specific dimension of resilience. This study aims to explore the underlying neural correlates of different operational definitions of resilience in the same participant using resting-state fMRI. Fifty-eight healthy university students in Hong Kong who underwent resting-state fMRI brain scanning were included. Their self-perceived overall, state and trait, and outcome-based resilience levelswere measured by different resilience scales. Multiple regression analyses were performed between the different measures of resilience and the whole-brain regional homogeneity (ReHo), and between resilience measures and long-range functional connectivity from both a whole-brain and a seed-based approach using fourteen preselected brain regions. The State Resilience Scale was found to be negatively associated with the ReHo of the hippocampus and parahippocampal gyrus. The outcome-based measure of resilience was negatively associated with the ReHo of the angular gyrus and insula. The Trait Resilience Scale was found to be negatively associated with the functional connectivity between the amygdala and inferior frontal gyrus from both a whole-brain and a seed-based approach. No overlapping regions or pathways were found, indicating that different operationalizations of resilience represent distinct areas of resilience.
Optimizing Anterior Urethral Stricture Assessment: Leveraging AI-Assisted Three-Dimensional Sonourethrography in Clinical Practice
Authors: Feng Chao , Lu Qi-Jie , Xue Jing-Dong , Shu Hui-Quan , Sa Ying-Long , Xu Yue-Min , Chen Lei
Published: May 2024

Purpose
This investigation sought to validate the clinical precision and practical applicability of AI-enhanced three-dimensional sonographic imaging for the identification of anterior urethral stricture.
Methods
The study enrolled 63 male patients with diagnosed anterior urethral strictures alongside 10 healthy volunteers to serve as controls. The imaging protocol utilized a high-frequency 3D ultrasound system combined with a linear stepper motor, which enabled precise and rapid image acquisition. For image analysis, an advanced AI-based segmentation process using a modified U-net algorithm was implemented to perform real-time, high-resolution segmentation and three-dimensional reconstruction of the urethra. A comparative analysis was performed against the surgically measured stricture lengths. Spearman’s correlation analysis was executed to assess the findings.
Results
The AI model completed the entire processing sequence, encompassing recognition, segmentation, and reconstruction, within approximately 5 minutes. The mean intraoperative length of urethral stricture was determined to be 14.452 ± 8.385 mm. Notably, the mean lengths of the urethral strictures reconstructed by manual and AI models were 13.092 ± 7.463 mm and 13.419 ± 7.216 mm, respectively. Interestingly, no statistically significant disparity in urethral stricture length between manually reconstructed and AI-reconstructed images was observed. Spearman’s correlation analysis underscored a more robust association of AI-reconstructed images with intraoperative urethral stricture length than manually reconstructed 3D images (0.869811 vs. 0.8201756). Furthermore, AI-reconstructed images provided detailed views of the corpus spongiosum fibrosis from multiple perspectives.
Conclusions
The research heralds the inception of an innovative, efficient AI-driven sonographic approach for three-dimensional visualization of urethral strictures, substantiating its viability and superiority in clinical application
Meta-SCI app: a comprehensive transcriptional reference for understanding the severity and progression of spinal cord injury
Authors: Grillo-Risco Rubén , Hidalgo Marta R. , Rojas Beatriz Martínez , Moreno-Manzano Victoria , García-García Francisco
Published: May 2024

Background
Spinal cord injury (SCI) is a devastating condition that leads to motor, sensory, and autonomic dysfunction. Current therapeutic options remain limited, emphasizing the need for a comprehensive understanding of the underlying SCI-associated molecular mechanisms.
Results
This study characterized distinct SCI phases and severities at the gene and functional levels, focusing on biomarker gene identification. Our approach involved a systematic review, individual transcriptomic analysis, gene meta-analysis, and functional characterization. We compiled a total of fourteen studies with 273 samples, leading to the identification of severity-specific biomarker genes for injury prognosis (e.g., Srpx2, Hoxb8, Acap1, Snai1, Aadat) and phase-specific genes for the precise classification of the injury profile (e.g., Il6, Fosl1, Cfp, C1qc, Cp). We investigated the potential transferability of severity-associated biomarkers and identified a twelve-gene signature that predicted injury prognosis from human blood samples. We also report the development of MetaSCI-app - an interactive web application designed for researchers - that allows the exploration and visualization of all generated results (https://metasci-cbl.shinyapps.io/metaSCI).
Conclusions
Overall, we present a transcriptomic reference and provide a comprehensive framework for assessing SCI considering severity and time perspectives, all integrated into a user-friendly tool.