bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Health Inequities Through Total Knee Arthroplasty: An Experience From Bhutan
Authors: Pradhan Nomina , Tamang Monu , Rai Sagar , Gyaltshen Choeda , Dema Choney , Mynak Mimi Lhamu , Canestrari Michael , Sands Kenneth Christopher , Wangdi Kuenzang
Published: February 2025

Background and Aims

Bhutan is a low–middle‐income country with a 0.7 million population with a high burden of musculoskeletal conditions. Recognizing the high burden of osteoarthritis, total knee arthroplasty (TKA) was launched in the country in 2022. However, Bhutan continues to refer complicated cases to India. In 2024, International Operation, a US‐based nonprofit secular and humanitarian organization, conducted a TKA camp in Bhutan. This perspective aims to report about the camp and discuss how such camps help reduce healthcare disparities.

Method

We compiled data on patients who underwent total knee or hip arthroplasty in last 7 years from the registry maintained at National Referral Hospital of Bhutan. We shared our experience of hosting TKA camp and discuss how such camps might help reduce healthcare disparities.

Result

In last 7 years, Bhutan referred increasing number of patients for total knee and hip arthroplasty to India. Royal Government of Bhutan spends Nu. 250,000 (approximately US$3000) per patient excluding expenses for travel, logistics, and medications. A team from International Operation conducted TKA on 31 patients during the camp.

Conclusion

Such camps would help reduce the healthcare disparities in low‐ and middle‐income countries.
Choosing the Path: Insights Into Zambian Medical Students' Specialty Selections
Authors: Musa Gerald , Chilawa Samuel , Bwanga Alick , Mwela Bupe Mumba , Chikoya Laston , Chaurasia Bipin
Published: February 2025

Background

The specialization of medical students is essential for enhancing healthcare quality, and meeting the diverse needs of patients, with medical training programs significantly influencing their career trajectories and expertise development. This study aimed to investigate the future specialty preferences of medical students from various medical schools in Zambia.

Materials and Methods

The study included participants from seven medical schools who had completed at least their first clinical clerkship. Data collection involved distributing structured questionnaires containing Likert scale items and open‐ended questions via an online Google Sheets platform. Data collected included: demographics, name of medical school, year of study, specialty preferences, factors influencing specialty preferences, awareness about medical specialties, and career pathways.

Results

A study involving 127 medical students in clinical clerkships revealed a gender ratio of 1.1:1 male to female, with 73% aged between 20 and 25 years. Specialty preferences varied, with internal medicine (12%) and cardiovascular surgery (10%) being popular choices, and 62% changing their preferences during clerkships. Key factors influencing specialty choice were personal interest (74%), work‐life balance (41%), and career prospects (30%). Only 21% were very familiar with medical specialties, and 83% rated mentorship availability poorly and suggested organizing workshops to enhance awareness. Future plans included further specialization (54%), international humanitarian work (54%), and medical academics (27%).

Conclusion

Despite recognizing the importance of mentorship, students rated the availability of mentorship and informational resources as inadequate. The findings emphasize the need for enhanced mentorship programs, comprehensive career guidance, and targeted informational workshops to support informed specialty choices, contributing to a better‐prepared and more satisfied medical workforce.
Acute Administration of 10 mg Methylphenidate on Cognitive Performance and Visual Scanning in Healthy Adults: Randomised, Double‐Blind, Placebo‐Controlled Study
Authors: Aitken Blair , Downey Luke A. , Rose Serah , Manning Brooke , Arkell Thomas R. , Shiferaw Brook , Hayley Amie C.
Published: February 2025

Objective

To examine the effect of a low dose (10 mg) of methylphenidate on cognitive performance, visuospatial working memory (VSWM) and gaze behaviour capabilities in healthy adults.

Methods

This randomised, double‐blind, placebo‐controlled and crossover study examined the effects of 10 mg methylphenidate on cognitive performance, VSWM and gaze behaviour. Fixation duration and rate, gaze transition entropy, and stationary gaze entropy were used to quantify visual scanning efficiency in 25 healthy adults (36% female, mean ± SD age = 33.5 ± 7.8 years, BMI = 24.1 ± 2.9 kg/m2). Attention, memory, and reaction time were assessed using the E‐CogPro test battery.

Results

Methylphenidate significantly enhanced performance in numeric working memory tasks, reflected by reduced errors and increased accuracy relative to placebo. No significant changes were observed in other cognitive or visual scanning metrics.

Conclusions

A low dose of methylphenidate improves limited domains of psychomotor speed and accuracy but does not affect visual scanning efficiency. This suggests limited usefulness as a general pro‐cognitive aid and raises the possibility of a lower threshold of effect for measurable psychostimulant‐induced changes to visual scanning behaviour. Further research is needed to explore these potential dose‐response relationships and effects across diverse populations.

Trial Registration

ACTRN12620000499987
Construction of the Single‐Cell Landscape of Hashimoto's Thyroiditis Tissue and Peripheral Blood by Single‐Cell RNA Sequencing
Authors: Song Kaiyu , Wang Xiaojie , Yao Wenjie , Wang Yuantao , Zhang Qinling , Tang Yuxiao , Mou Yakui , Song Xicheng , Zhou Jin
Published: February 2025

Background

Hashimoto's thyroiditis (HT) is the most common organ‐specific autoimmune disease, and its etiology may be related to genetic, environmental, and epigenetic factors. However, its exact pathogenesis remains elusive.

Methods

In this study, single‐cell transcriptomic sequencing and bioinformatics analysis were performed on the thyroid tissues of six HT patients, peripheral blood mononuclear cells (PBMCs) of four HT patients, and normal thyroid tissue of one healthy control. A panoramic single‐cell atlas of HT was constructed to explore changes in the abundance of different cell subsets in the states of the disease.

Results

A single‐cell atlas of HT was constructed, and eight cell types were defined based on the marker genes. Subsequent clustering analysis of T cells, B cells, myeloid, and thyroid follicular cells revealed that the abundance rates of the CD8+T_CCL4L2, B_MEF2B_BCL6, Mac_APOE, Mac_IL1B, and TFC_PAX8_NKX2‐1 subgroups were elevated in thyroid tissues of HT patients. However, the abundance rate of the NKT_KLRD1_KLRC2 subgroup was risen in the PBMCs of HT patients. Ig‐producing plasma cells were specifically enriched in the B‐cell subgroup.

Conclusion

The present study further validated the role of immune cells in the pathogenesis of HT at the cellular level. In addition, a new cell subset B_MEF2B_BCL6 was found. It could be speculated that MEF2B mainly transactivates the expression level of the transcriptional repressor BCL6, leading to the development of HT. A new cell subset TFC_PAX8_NKX2‐1 was also identified, in which the specific transcription factors PAX8 and NKX2‐1 were highly expressed in HT tissues.
Strengthening evidence‐based intrapartum and newborn care practices in medical schools: Subnational implementation research from India
Authors: Gupta Madhu , Iyengar Kirti , Singla Neena , Kaur Kiranjit , Verma Madhur , Sethi Adhish Kumar , Singla Rimpi , Rohilla Minakshi , Suri Vanita , Aggarwal Neelam , Singh Tarundeep , Pal Swarnika , Dhiman Anchal , Goel Poonam , Goel N. K. , Pant Reena , Gaur Kusum Lata , Gehlot Hanslata , Bhati Indra , Verma Manoj , Agarwal Sudesh , Acharya Rekha , Singh Keerti , Chauhan Madhubala , Rastogi Radha , Bedi Renu , Pachori Purnima , Nayak Bipin , Modi Bhavesh , Nakum Kanaklata , Trivedi Atul , Aggarwal Shonali , Patel Sangita , Sharma Nirmala , Sharma Mamta , Meena Khushbu
Published: February 2025

Objective

We examined the impact of a codesigned multicomponent implementation strategy on adherence to evidence‐based intrapartum care, respectful maternity care, and newborn care practices in 11 medical schools across two states and a union territory in India.

Methods

We conducted pre‐post implementation research using the reach, effectiveness, adoption, implementation, and maintenance (RE‐AIM) framework from July 2019 to October 2021. The implementation strategy was codesigned by researchers and medical school faculty. At baseline and endline, we recruited intranatal (n = 175, 158) and postnatal women (n = 158, 167) with uncomplicated vaginal delivery for observation and interview, respectively. The primary outcome was proportion of uncomplicated deliveries with a composite of avoiding augmentation, avoiding episiotomy, and using alternate birthing positions. We used generalized estimating equations to compare baseline and endline findings and estimated adjusted prevalence odds ratios (APORs).

Results

The primary outcome increased from 5.4% at baseline to 17.4% at endline with APOR 3.55 (95% CI: 1.08, 11.66). A decline was observed in not‐recommended practices, namely pubic shaving (APOR 0.05, 95% CI: 0.01, 0.18), enema (APOR 0.07, 95% CI: 0.02, 0.22), fundal pressure (APOR 0.05, 95% CI: 0.02, 0.14), episiotomy (APOR 0.75, 95% CI: 0.38, 1.48). Newborn care practices showed the greatest improvements in early initiation of breastfeeding (APOR 42.35, 95% CI: 5.70, 314.61) and delayed cord clamping (APOR 21.28, 95% CI: 6.00, 75.43). Results from postnatal interviews corroborated those from direct observation in the labor room.

Conclusion

A codesigned multi‐component implementation strategy can improve adherence to evidence‐based intrapartum and newborn care practices in medical schools.
A human skin microbiome reference catalog and the skin microbial landscape of plateau adults
Authors: Liu Yi , Li Zhiming , Zhang Chao , Li Bo , Jiang Weiwei , Li Hang , Zhang Lei , Zhen Hefu , Bao Shujun , Li Xiong , Liu Yinuo , Chen Xianzhen , Du Jinxia , Xia Jingjing , Wang Jiucun , Guo Ruijin , Sun Yuzhe , Pan Bo , Lei Wenzhi , Xiao Liang , Zhao Jin , Jin Xin , Zhang Wenwei , Liu Xiaogang , Wang Jian , Chen Min , Liao Wanqing , Fang Wenjie , Nie Chao , Pan Weihua
Published: February 2025

Comprehensive reference genomes are needed for the classification and functional characterization of the human skin microbiota. Here, we established human skin microbiome genome (HSMG) and protein (HSMP) catalogs by integrating 739 newly sequenced and 2,520 published samples, along with two published microbial genome catalogs. The HSMG includes 3547 prokaryotic species, of which 1556 (43.87%) are unidentified, and the HSMP contains 39,283,339 nonredundant proteins, with 64.8% of which are poorly characterized. Using the HSMG as a reference, we identified distinct features and biogeographical traits of the skin microbiome in plateau adults, revealing significant differences between sebaceous and dry skin, with 1784 of 3547 inferred prokaryotes showing considerable variation. Additionally, host characteristics, skincare, and daylight habits were found to shape the skin microbiome. This work expands our understanding of the diversity of uncultured skin bacteria and provides a comprehensive characterization of the human skin microbiome in plateau environments.
Remediation of the picture‐text problem for learners exhibiting reading deficits
Authors: Lewis Taylor K. , Cariveau Tom
Published: February 2025

Early reading materials are replete with pictures. Pictures purportedly improve reading comprehension and motivation; however, the simultaneous presentation of pictures and text can also impede textual control for some readers. Attempts to remediate restricted stimulus control in picture–text compounds suggest that omitting the picture element is most effective, although these arrangements may also be less socially valid. The current study is an evaluation of a novel compound stimulus prompt (CSP) arrangement that required that the learner differentially respond to the underselected (i.e., textual) element during picture‐book reading. The development of textual control in this condition was compared with that in text‐only and picture prompt arrangements. The CSP condition required the same or fewer sessions to produce textual control as the text‐only condition for five out of six participants who exhibited reading difficulties. Participants emitted more correct responses during CSP and picture prompt instruction and preferred these conditions to the text‐only condition during a concurrent‐chains assessment.
Impact of pharmacist management on chronic obstructive pulmonary disease in a family medicine residency clinic
Authors: Figueras Jacqueline Elaine , Putnam Christina , Wong Carolyn , Bagheri Sholeh , Darr Marilyn , Vander Weide Luke A
Published: February 2025

Introduction

Studies support pharmacist intervention to improve adherence and reduce hospital admissions in the management of chronic obstructive pulmonary disease (COPD); however, evidence is lacking to assess pharmacist management on symptom improvement and disease control using COPD Assessment Test (CAT) scores in a primary care setting.

Objective

The purpose of this study was to assess the impact of pharmacist involvement in performing spirometry and therapeutic management of COPD on symptoms and inhaler use.

Methods

This was a prospective cohort study of patients with COPD at a family medicine residency clinic from January 2021 to November 2022. Patients included were 18 years of age or older, had a confirmed diagnosis of COPD with spirometry, and completed at least one COPD management visit with the pharmacist. Pharmacists performed spirometry, modified inhaler therapy, provided COPD and inhaler education, reviewed and ordered immunizations and labs, and provided tobacco cessation education and management if applicable. The primary outcome was the change in CAT scores from baseline to 3 months. The secondary outcome was the percentage of patients on guideline‐directed inhaler therapy at 3 months compared with baseline.

Results

A total of 77 spirometry visits were completed by the pharmacist, with confirmed COPD in 49 patients who were managed by the pharmacist and included in the final analysis. At baseline, the average age was 66 years old, 53% were males, and only 6% had no smoking history. The mean CAT score improved by 5.0 points (p < 0.001) from baseline. At baseline, 45% were on guideline‐directed therapy, which increased to 98% at final follow‐up (p < 0.001).

Conclusion

This study assessed the impact of pharmacist‐led spirometry and COPD management at a family medicine residency clinic. Based on the results, pharmacist involvement in COPD management resulted in an improvement in symptoms and increased use of guideline‐directed inhaler therapy.
Amniotic Membrane‐Derived Extracellular Matrix for Developing a Cost‐Effective Xenofree Hepatocellular Carcinoma Organoid Model
Authors: Atta Dina , Abou‐Shanab Ahmed M. , Kamar Samaa Samir , Soliman Mariam Waleed , Magdy Shireen , El‐Badri Nagwa
Published: February 2025

Current limitations in the treatment of hepatocellular carcinoma (HCC) include tumor recurrence, chemoresistance, and severe side effects, all of which call for novel cancer models that better represent the tumor microenvironment (TME). 3D organoids hold promise due to their increased relevance to the TME hallmarks. Herein, we aim to establish an HCC organoid model that mimics the HCC microenvironment and its metabolic interactome. The organoid comprises a decellularized human amniotic membrane (dAM) as a biomimetic matrix, Huh‐7 cell line, bone marrow mesenchymal stromal cells (BM‐MSC), and human umbilical vein endothelial cell‐conditioned medium (HUVEC‐CM). The structure integrity of the HCC organoid was monitored using H&E staining at 7, 14, and 21 days and transmission electron microscopy (TEM) and scanning electron microscopy (SEM) at 21 days. The established organoid model maintained its viability over 21 days as tested by propidium iodide (PI) fluorescence staining, MTT, upregulated expression of proliferating cell nuclear antigen (PCNA), and alpha‐fetoprotein (AFP). The expression of vascular endothelial growth factor (VEGF) in the HCC organoid induced a neo‐angiogenic response in ovo. Metabolic reprogramming in the HCC organoid showed a shift toward glycolysis as indicated by promoted glucose consumption, upregulated lactate production, and reduced cellular pyruvate concentration. Oxidative phosphorylation was suppressed as indicated by reduced reactive oxygen species (ROS), and hydrogen peroxide (H2O2), and halted urea cycle progression. The dataset shows that the dAM may hold a promise for its use as extracellular matrix (ECM) source for HCC organoid models, by replicating the HCC microenvironment and metabolic signature, thus holding a promise for developing targeted therapeutic strategies.
Process‐Dependent Variations in the Proliferation of Myoblasts, Fibroblasts and Chondrocytes on Laser‐Sintered Polypropylene
Authors: Detsch R. , Schlicht S. , Nawaz Q. , Boccaccini A. R. , Drummer D.
Published: February 2025

Additively manufactured polyolefins find broad applications in medical engineering, enabling the manufacturing of patient‐specific geometries. For investigating the influence of processing conditions of laser sintered locally macroporous polypropylene substrates, the response of myoblasts, chondrocytes, and fibroblasts has been characterized in this study. An influence of the applied manufacturing parameters on the attachment and viability of the investigated cells is observed, showing the effect of the superficial pore topology on the attachment and the spreading of cells. The viability and attachment of fibroblasts and chondrocytes could be improved by reducing the thermal exposure during the processing step of the dense base part, associated with increased superficial porosity and the corresponding increase of the surface area. The applied additive manufacturing process of macroporous structures influences emerging cell morphologies, leading to an extended morphological expression of chondrocytes and the overgrowth of small pores by fibroblasts. This indicates an improvement in superficial cell adhesion due to larger pores. These findings indicate the significance of the processing conditions in laser sintering of polypropylene on the cell response through the optimization of processing parameters and the attachment of an open‐cell pore structure.
Metal Dimers‐Doped h‐BN Structures as Novel Toxic Gases Sensors With Enhanced Sensitivity Properties: An ADFT Study
Authors: Cruz‐Martínez H. , Rojas‐Chávez H. , Santiago‐Silva L. , López‐Sosa L. , Calaminici P.
Published: February 2025

Toxic gases monitoring and detection are fundamental to lessening public health problems. Therefore, in this work, to explore emergent sensor materials, 3d‐metal dimers‐doped hexagonal boron nitride (h‐BN) structures were investigated employing auxiliary density functional theory (ADFT) as novel CO and NO gas sensors. Firstly, the stabilities of Co2, Ni2, and Cu2 dimers deposited on defective h‐BN were determined. Then, sensitivities of 3d‐metal dimers‐doped h‐BN structures towards the NO and CO gases were investigated. It was found that the interaction energies of these 3d‐metal dimers embedded on defective h‐BN are higher than those deposited on pristine h‐BN structure, which indicates that the 3d‐metal dimers exhibit good stability on defective h‐BN. Moreover, this work demonstrated that the CO and NO adsorption energies on 3d‐metal dimers‐doped h‐BN structures are higher than those computed in the literature for pristine h‐BN structure. Consequently, the here considered 3d‐metal dimers‐doped h‐BN structures can be good candidates for toxic CO and NO gas detection.
Interventions to Reduce Food and Nutrition Insecurity Among Dental Students
Authors: Touger‐Decker Riva , Sabato Emily , Singer Steven R. , Zelig Rena , Toth Steven , Marshall Teresa , Sackey Joachim
Published: February 2025

Purpose/Objective

The prevalence of food insecurity (FI) on university campuses is increasing. This study explored the prevalence of food and nutrition insecurity (NI) among dental students and barriers and interventions to address them.

Methods

A cross‐sectional web‐based survey was conducted. Validated tools were used to assess FI and NI. Univariate binary logistic regressions and a multivariable logistic regression model identified factors independently associated with FI.

Results

The response rate was 11.9% (n = 67). The mean age was 28.4 years; 67% were D1/D2 students; 53.7% were female, 15.2% identified as Hispanic, and 50.7% as White. Forty percent experienced FI; 24.2% had low nutrition security (NS), and 26.9% reported partial or full responsibility for others' living expenses. Twenty‐four percent were married, 25.8% used a food pantry; 11.1% had unsuccessfully applied for Supplemental Nutrition Assistance Program benefits. In the adjusted model, low NS, nonmarried status, and food pantry use increased the likelihood of FI (odds ratios of 16.854, 10.182, and 9.123, respectively). Common barriers and potential interventions to address FI and NI were explored.

Conclusions

The prevalence of FI in this sample was greater than the national average. Those who were unmarried, had low NS, and used a food pantry were significantly more likely to have FI. Proposed interventions include student services enhancements and curriculum modifications on nutrition and wellness. Further research is necessary with a larger sample to understand factors contributing to NI and FI among dental students.
Responses to Hypoxia and Hyperoxia in Embryonic Tiger Keelbacks (Rhabdophis tigrinus lateralis; Colubridae)
Authors: Li Xiang‐Mo , Su Shan , Zhang Lu‐Wen , Wu Yan‐Qing , Ji Xiang
Published: February 2025

Studies examining the oxygen dependency of embryonic survival, growth, and differentiation have been conducted for decades in a diverse array of animal taxa but including only one oviparous snake, the viperine water snake Natrix maura. Here, we describe a study incubating eggs of the tiger keelback Rhabdophis tigrinus lateralis (Colubridae) under four oxygen conditions, hypoxia (7% and 11% O2), normoxia (21% O2), and hyperoxia (31% O2), for different lengths or at different stages of incubation. The length of hypoxic exposure is important in affecting embryonic development in R. t. lateralis, with prolonged hypoxic exposure retarding embryonic growth and differentiation, increasing embryonic mortality and deformity, reducing hatchling size and mass, and altering hatchling body shape relative to normoxic controls. Embryonic tiger keelbacks are most susceptible to hypoxia late in development, as revealed by the fact that a 5‐day exposure of eggs to hypoxia of 7% O2 reduced embryo mass and hatchling mass if it occurred at late stages of incubation. Hyperoxia of 31% O2 did not enhance development of R. t. lateralis embryos, only affecting hatchling head width, which slightly differed between hyperoxic hatchlings and their normoxic siblings. This study demonstrates the importance of avoiding hypoxic exposure at late stages of embryonic development in snakes.
Intramedullary erythrophagocytosis in myelodysplastic syndrome with heterozygous U2AF1 Q157R variant
Authors: Krishnamurthy Kritika , Shastri Aditi , Wang Yanhua
Published: February 2025

This report highlights a somewhat unique case of U2AF1 mutated myelodysplastic syndrome (MDS) with morphological evidence of increased intramedullary erythrophagocytosis, in the absence of obvious clinical signs of hemolysis. These findings merit investigation in a larger cohort of U2AF1 mutated MDS cases to further delineate the morphological spectrum of ineffective intramedullary hematopoiesis and nonimmune hemolysis, including features distinctive to S34 and Q157 variants.
Therapeutic Versus Non‐Therapeutic Dose Anticoagulation in COVID‐19 Infection: A Systematic Review and Meta‐analysis of Randomised Controlled Trials
Authors: Selvarajan Sushil , John Jisha Sara , Tharyan Prathap , Kirubakaran Richard , Singh Bhagteshwar , George Biju , Mathew Joseph L. , Rupali Priscilla
Published: February 2025

Background

Abnormal coagulation and thrombotic complications prompted many guidelines to recommend thromboprophylaxis for patients hospitalised with COVID‐19, but the dose required for prophylaxis remains unclear. This systematic review (SR) analyses the safety and efficacy of therapeutic dose anticoagulation (TDA) versus non‐therapeutic dose anticoagulation (NDA) in COVID‐19 patients.

Methods

According to the Cochrane Handbook of Systematic Review of Interventions, we performed an SR. The protocol is registered in Prospero (CRD42021269197, date 12 August 2021).

Results

In this SR of 18 studies, TDA was shown to reduce all‐cause mortality (risk ratio [RR] 0.83; 95% confidence interval [95% CI] 0.70, 0.99) in COVID‐19 infection. TDA also reduced thrombosis (RR 0.55; 95% CI 0.48, 0.72) but increased major bleeding (RR 1.87; 95% CI 1.29, 2.69). A stratified analysis according to severity revealed that, in non‐critical patients, TDA resulted in mortality benefit (RR 0.79; 95% CI 0.67, 0.94). In critical patients, TDA did not affect all‐cause mortality (RR 1.03; 95% CI 0.89, 1.18) but reduced thrombosis (RR 0.65; 95% CI 0.48, 0.86) and increased major bleeding (RR 1.85; 95% CI 1.06, 3.23).

Conclusion

TDA significantly reduced all‐cause mortality and thrombosis in non‐critical COVID‐19 patients at the expense of increased major bleeding. In critical COVID‐19, this mortality benefit was not observed.
Methodological progress note: Longitudinal qualitative research and applications to hospital medicine
Authors: Orr Andrew R. , Balmer Dorene F.
Published: February 2025

Longitudinal qualitative research (LQR) is an emerging methodology in healthcare and health professions education research that focuses on change in complex, dynamic transitions, and processes as that change unfolds. This approach allows for in‐depth exploration of personal and professional transitions, developmental processes, and evolution in how individuals make sense of experiences and events. In this Methodological Progress Note, we define the key features of LQR, distinguish LQR from other qualitative methodologies, and present a case for longitudinal qualitative work to offer a lens of time that might illuminate gaps in the field of hospital medicine.
RSV‐Bacterial Co‐Infection Is Associated With Increased Illness Severity in Hospitalized Children ‐ Results From a Prospective Sentinel Surveillance Study
Authors: Torres Ana Rita , Gaio Vânia , Melo Aryse , Lança Miguel , Barreto Marta , Gomes Licínia , Azevedo Inês , Bandeira Teresa , Lito David , Guiomar Raquel , Rodrigues Ana Paula ,   VigiRSV group
Published: February 2025

During the autumn/winter respiratory syncytial virus (RSV) epidemics, bacterial co‐infection is common and affects the disease severity. We aimed to understand the relationship between RSV‐bacterial co‐infections and clinical severity since the RSV seasonality change after COVID‐19 pandemic. We conducted a prospective, sentinel surveillance study at 20 sites in Portugal in children under 2 years hospitalized with RSV, between April 21 and January 23. Effect of co‐infection with potentially pathogenic bacteria (PPB) on the length of hospitalization and disease severity was investigated using multivariate linear and log‐binomial regression models. Among 678 RSV hospitalizations, 67.4% occurred in children under 6 months and 15.3% in preterm; 20.4% tested positive for PPB; median length of hospitalization was 5 days (IQR: 3–7days). Children coinfected with PPB had a higher rate of ICU admission (29.7% vs. 3.5%, p < 0.001), resulting in more prolonged hospitalizations (7 vs. 5 days, p < 0.001) and a 13‐fold risk of having severe disease (RR: 13.2, 95% CI:7.3–23.9). RSV‐bacterial co‐infection was associated with increased length of hospitalization and severe illness during off‐season epidemics. This risk is probably overestimated, as laboratory testing for bacterial infections is usually higher in severely ill‐appearing children. Measures to prevent outgrowth of pathogenic bacteria within the respiratory tract should be discussed.
The Novel Oncolytic Herpes Simplex Virus Type‐1 (HSV‐1) Vaccine Strain VC2 Constitutively Expressing GM‐CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1/Balb/c Mouse Model of Stage Four Breast Cancer
Authors: Nabi Rafiq , Chouljenko Vladimir N. , Musarrat Farhana , Davis Megan E. , Mohan Harikrishnan , Ghavimi Reza , Stanfield Brent , Dutta Ojasvi , Kousoulas Konstantin G.
Published: February 2025

Oncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type‐1 (HSV‐1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV‐1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) gene inserted in place of HSV‐1 Glycoprotein C (gC). We tested the efficacy of VC2‐GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM‐CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 104 plaque forming units (PFU) of VC2/VC2‐GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2‐GMCSF compared to VC2 or mock treatment. VC2‐GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2‐GMCSF treated animals, which was associated with reduced pro‐tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM‐CSF enhanced the overall efficacy of VC2 for OVT. VC2‐GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers.
Systematic Reevaluation of Repurposed Drugs Against the Main Protease of SARS‐CoV‐2 via Combined Experiments
Authors: Ye Jiankai , Zhang Rui , Zhou Jiahao , Xu Tao , Liu Xiaoping , Chen Yunyu
Published: February 2025

The main protease (Mpro) of SARS‐CoV‐2 is an attractive drug target for antivirals, as this enzyme plays a key role in virus replication. Drug repurposing is a promising option for the treatment of coronavirus disease 2019 (COVID‐19). Recently, a number of FDA‐approved drugs have been identified as Mpro inhibitors, but stringent hit validation is lacking. In this study, we rigorously reevaluated the in vitro inhibition of the Mpro enzyme by repurposed drugs via combined experiments, including the fluorescence resonance energy transfer (FRET) assay, fluorescence polarization (FP) assay, and protease biosensor cleavage assay. Our results from a set of in vitro assays revealed that boceprevir is a potential Mpro inhibitor, but other repurposed drugs, including atazanavir, dipyridamole, entrectinib, ethacridine, glecaprevir, hydroxychloroquine, ivermectin, meisoindigo, pelitinib, raloxifene, roxatidine acetate, saquinavir, teicoplanin, thonzonium bromide, and valacyclovir, are not. Our research highlights that the use of candidate Mpro inhibitors from primary screening warrants further comprehensive studies before the reporting of new findings.
Quiet Workaholics? The Link Between Workaholism and Employee Silence and Moral Voice as Explained by the Social‐Cognitive Theory of Morality
Authors: Knoll Michael , Fida Roberta , Marzocchi Ivan , Searle Rosalind H. , Connelly Catherine E. , Ronchetti Matteo
Published: February 2025

When employees engage in potentially harmful behavior, organizations and societies rely on others to voice these issues. We propose that workaholism, a way that some individuals develop to deal with and thrive in today's intense and demanding work environment, reduces these individuals' intention to engage in moral voice and increases employee silence. Drawing on social‐cognitive theory of morality, we propose that this occurs because workaholism, being driven by an inner compulsion to working extensively, disengages moral self‐regulation which, in turn, affects both the activation of moral behavior (i.e., voice intentions) and the inhibition of immoral behavior (i.e., employee silence). Further, based on social‐cognitive theory's premise that moral behavior is jointly regulated by personal and social standards, we propose that a context that endorses this inner pressure to work (i.e., climate of self‐interest) strengthens the relationship between workaholism and moral disengagement. Findings from two three‐wave time‐lagged studies of Italian and UK employees suggest that workaholism—but not workload—is associated with moral disengagement and indirectly with more silence and less moral voice intention. Additionally, Study 2's moderated‐mediation model showed that perceived climate of self‐interest moderates the relationship between workaholism and moral disengagement and revealed dimension‐specific effects of workaholism.
Paracrine Influence of Masquelet's Induced Membrane on Marrow Derived Mesenchymal Stem Cells
Authors: Bowman Meredyth , Sclamberg Gracie , Wessels Emma , Cragg Kyle , Donneys Alexis , Hankenson Kurt D. , Hake Mark E. , Alford Andrea I.
Published: February 2025

Masquelet's induced membrane technique (MIMT) is a staged surgical procedure that leverages the foreign body induced membrane (IM) that forms around a cement spacer placed into a segmental bone defect to support subsequent bone grafting. The mechanisms by which the IM supports bone consolidation are not fully understood. We present an indirect coculture system for studying IM‐MSC interactions using a rat model of MIMT. Compared to control cells, MSC Tnap (alkaline phosphatase) was induced by 4‐ but not 8‐week IM. MSC Spp1 (Osteopontin) was attenuated by both 4‐ and 8‐week IM. Although Tnfrsf11b (osteoprotegrin) in MSC exposed to IM was not different from control cells, it was induced by 8‐week IM compared to 4‐week IM. MSC Tnfsf11 (RANKL) was reduced by 4‐week and 8‐week IM. MSC Thbs2 (Tsp2) was induced by 8‐week but not 4‐week IM. Ablation of macrophages in IM blocked the induction of Thbs2 by 8‐week IM. MSC Col1a1 expression was not affected under any condition tested. TMT proteomics analysis of IM‐conditioned medium revealed 150 unique secreted proteins, 7 of which were differentially abundant (fold change ≥ 2 and FDR corrected p ≤ 0.05) in 8‐week versus 4‐week IM secretomes. All differentially abundant proteins were elevated in medium conditioned by 8‐week IM. Our data suggest that factor(s) secreted by IM resident cells affect MSC gene expression, and that duration of IM development influences the potency and nature of this paracrine effect. Patient‐specific factors including age and interval between MIMT surgeries may affect IM biological potency and graft to bone consolidation.
Involvement of Nerve Growth Factor in the Reparative Reaction to Osteonecrotic Lesions
Authors: Ayabe Yusuke , Motomura Goro , Yamaguchi Ryosuke , Utsunomiya Takeshi , Tanaka Hidenao , Sakamoto Kosei , Nakashima Yasuharu
Published: February 2025

The reparative zone in femoral head osteonecrosis is pivotal for repair; however, the repair response mechanism remains poorly understood. Although neurotrophic nerve growth factor significantly contributes to bone formation in fatigue fractures and ectopic ossification, the relationship between nerve growth factor and the repair response to osteonecrosis remains unexplored. We aimed to elucidate the role of nerve growth factor in osteonecrosis repair. Twenty‐seven wholly resected femoral heads diagnosed with Japanese Investigation Committee Stage 3 femoral head osteonecrosis, excluding those with severe collapse, were analyzed. Histopathological diagnosis confirmed the presence of necrotic, reparative, and viable zones in all examined femoral heads. Quantitative evaluation of immunohistological staining, including nerve growth factor, vascular endothelial growth factor, osteocalcin, CD31, and TUBB3, was conducted in each zone. Additionally, micro‐computed tomography was used to measure the trabecular bone microstructure in the reparative zone. Nerve growth factor expression was detected in all 27 femoral heads with osteonecrosis, exhibiting a significantly higher prevalence in the reparative zone than in other regions (p < 0.0001). Nerve growth factor was predominantly distributed on the necrotic side within the reparative zone, rather than the viable side. In the reparative zone, nerve growth factor expression was positively correlated with bone formation parameters derived from micro‐computed tomography images. Vascular endothelial growth factor, osteocalcin, CD31(+) vascular endothelial cells, and TUBB3(+) nerve cells also significantly increased in the reparative zone. In conclusion, nerve growth factor expression was consistent across all femoral heads with osteonecrosis and may play a role in reparative reaction to osteonecrotic lesions.
Performance of GLIM with different nutrition risk screening tools in predicting 90‐day mortality in critically ill adults with acute stroke: A comparison study
Authors: Li Junzhuo , Li Xin , Yang Jiajia , Wang Yaqi , Gong Wenmei
Published: February 2025

Background

The Global Leadership Initiative on Malnutrition (GLIM) proposes a diagnostic process for malnutrition, including initial screening with nutrition screening tools, followed by diagnostic evaluation. This study aimed to compare the performance of GLIM with different nutrition screening tools in predicting 90‐day mortality in adults who are critically ill with acute stroke.

Methods

A comparative study was conducted on 308 adults (who critically ill) with acute stroke. Multiple nutrition screening tools were evaluated upon admission. Nutrition status was assessed using GLIM criteria. The predictive performance of GLIM on mortality was analyzed using Cox regression.

Results

The prevalence of malnutrition ranged from 17.86% to 28.25%, depending on the nutrition screening tools used for classification. During 90‐day of follow‐ups, 112 (36.36%) deaths occurred. GLIM effectively predicted 90‐day mortality, with GLIM and the modified Nutritional Risk in the Critically Ill (mNUTRIC) screening demonstrating the best predictive ability [Hazard Ratio: 2.807 (1.816–4.339)].

Conclusion

Malnutrition identified by GLIM with mNUTRIC demonstrates a good ability to predict mortality in critically ill adults with acute stroke. GLIM criteria anticipate mortality and might guide interventions, with important implications for clinical practice and research.
A Deterministic Model of the Gamma Radiation at the Soil Surface–Including Soil Moisture Correction for Better Radiation Data Exploitation in Soil Mapping
Authors: Herrmann Ludger , Zimmermann Georg
Published: February 2025

Background

During the last decades, gamma spectrometry data have increasingly been used in soil science, for example, for mapping. However, the full data potential could not be exploited due to certain constraints, among which the insufficient representation of attenuating materials (in particular, water) in correction algorithms is the most important one. Due to this problem, most often only the potassium/thorium intensity ratio is used in soil science.

Aim

However, the ultimate goal must be to derive from field gamma spectrometry the real content of the chemical elements that can be sensed (i.e., normally , , , and ). The first enabling step is to deterministically model the gamma radiation at the soil surface in order to subsequently allow for water content correction by reverse modelling.

Methods

We present here a realisation of a mathematical model that is based on the ‘King‐equation’, but additionally introduces the soil science concept of horizons, that is, a finite number of strata of various vertical thicknesses, with homogeneous properties within each horizon. This approach allows the use of radial symmetry as concept for the three‐dimensional integration of the gamma signal. Input data for the model are horizon vertical thickness, total content of radiating and attenuating materials, and bulk density. Additionally, used parameters concern the decay chains of the radioactive elements.

Results

Model tests with real soil produced count rates in the expected order of magnitude. Due to the instrumental setup of the field spectrometer, it was necessary to replace full spectrum analysis by the concept of regions of relevance (ROR) in order to be able to compare the counts predicted by our model and the counts registered by the spectrometer. The ROR concept is based on the computation of the relevant elements' decay steps and includes Compton scattering.

Conclusion

Using this approach, a deviation between modelled and measured gamma radiation is reasonable for and . The reasons for still larger deviations with respect to the ‐signal are discussed.
Eosinophilic esophagitis associated with infliximab therapy in pediatric patients with inflammatory bowel disease
Authors: Wu Meng‐Che , Glickman Jonathan N. , Winter Harland S.
Published: February 2025

What's Known

The association between tumor necrosis factor antagonist and eosinophilic gastrointestinal disorders, including eosinophilic esophagitis is reported.

There is a potential association between the initiation of IFX therapy for some IBD patients and the subsequent development of EoE.

What's New

This case series of IBD patients who developed eosinophilic esophagitis post‐infliximab (IFX) therapy, highlights their demographic characteristics, clinical features, and comorbidities.

IFX might trigger a Th2 cytokine shift, leading to eosinophilic infiltration. Long‐term safety data are needed to identify outcomes in patients who develop eosinophilic esophagitis after treatment with TNF‐alpha antagonists.
Feeding hope: A quality improvement initiative to improve identification of food insecurity
Authors: Misner Nicole , Panagos‐Billiris Patoula , Yavelow Michelle , Chaphalkar Chaitanya , Tsalatsanis Athanasios , Khalaf Racha T.
Published: February 2025

Objectives

Food insecurity (FI), limited or uncertain access to adequate food, impacts every state, county, and community in the United States. The goals of this quality improvement (QI) initiative were to first achieve greater than 90% compliance with FI screening for patients seen at pediatric GI clinics within 1 year and second increase the proportion of families identified as FI connected with resources to 50% at follow‐up visits.

Methods

Using plan‐do‐study‐act cycles, interventions were implemented to (1) educate, (2) create a screening process, (3) optimize communication with EMR utilization, and (4) connect families to resources. Descriptive statistics on all variables collected were performed. Differences between the FI and food secure groups were assessed using the Mann–Whitney test for continuous variables and the Chi‐squared test for categorical variables. QIMacros® Quality Improvement/SPC Software for Excel was used to create process control charts to show improvement.

Results

During the timeframe from August 29, 2022, to February 29, 2024, 2946 visits were completed in the GI clinic, and 58% (1731 patients) were screened for FI. Of the patients that were screened for FI, 13% screened positive. Compliance with FI screening improved to 90%, and connection to resources improved to 75%. Race, ethnicity, preferred language, and insurance were all significantly associated with FI, p < 0.001

Conclusions

This QI initiative demonstrates standardized FI screening improves FI identification and connection to resources.
First Dimension Trap‐and‐Elute Combined with Second Dimension Reversed‐Phase Liquid Chromatography Separation Using a Two‐Dimensional‐Liquid Chromatography‐Tandem Mass Spectrometry System for Sensitive Quantification of Human Insulin and Six Insulin Analogs in Plasma: Improved Chromatographic Resolution and Stability Testing
Authors: Sistik Pavel , Urinovska Romana , Handlosova Klara , Handlos Petr , Andelova Katerina , Jurica Jan , Stejskal David
Published: February 2025

Multidimensional chromatography coupled to tandem mass spectrometry (MS/MS), including simple sample preparation with protein precipitation, anion conversion with ammonium hydroxide, and solid‐phase extraction using mixed‐mode anion exchange in a 96‐well plate format, has been validated for rapid simultaneous analysis of human insulin and its six analogs (lispro, glulisine, glargine, degludec, detemir, and aspart) in human plasma. This method is critical for clinical diagnostics, forensic investigations, and anti‐doping efforts due to the widespread use of these substances. In the present study, improved chromatographic resolution was achieved using a first‐dimension trap‐and‐elute configuration with an XBridge C18 (2.1 × 20 mm, 3.5 µm) trap column combined with second dimension separation on a Cortecs Ultra‐High‐Performance Liquid Chromatography (UHPLC) C18+ (2.1 × 100 mm, 1.6 µm) analytical column implemented within a two‐dimensional‐LC‐MS/MS system. The total chromatographic run time was 11 min. This setup increases both the resolution and sensitivity of the method. A mobile phase consisting of 0.8% formic acid (FA) in water and 0.7% FA in acetonitrile was used for gradient elution. Bovine insulin was used as the internal standard. MS detection was performed in positive electrospray ionization mode, and the ion suppression due to matrix effects was evaluated. Validation criteria included linearity, precision, accuracy, recovery, lower limit of quantitation, matrix effect, and stability tests with and without protease inhibitor cocktail under different conditions (short‐term stability, long‐term stability, and freeze‐thaw stability). The concentration range for all insulins was 50–15 000 pg/mL, with limits of quantification below the therapeutic reference range for all analytes. Intra‐run precision ranged from 1.1% to 5.7%, inter‐run precision from 0.7% to 5.9%, and overall recovery from 96.9% to 114.3%. The validated method has been implemented successfully by the Department of Forensic Medicine at our hospital for the investigation of unexplained deaths.