bluuebunny/crossref_metadata_2025 huggingface dataset:
Annual epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data
Authors: Kajos Luca Fanni , Molics Bálint , Elmer Diána , Pónusz-Kovács Dalma , Kovács Bettina , Horváth Lilla , Csákvári Tímea , Bódis József , Boncz Imre
Published: May 2024

Background

Health services utilization related to hip osteoarthritis imposes a significant burden on society and health care systems. Our aim was to analyse the epidemiological and health insurance disease burden of hip osteoarthritis in Hungary based on nationwide data.

Methods

Data were extracted from the nationwide financial database of the National Health Insurance Fund Administration (NHIFA) of Hungary for the year 2018. The analysed data included annual patient numbers, prevalence, and age-standardized prevalence per 100,000 population in outpatient care, health insurance costs calculated for age groups and sexes for all types of care. Patients with hip osteoarthritis were identified using code M16 of the International Classification of Diseases (ICD), 10th revision. Age-standardised prevalence rates were calculated using the European Standard Population 2013 (ESP2013).

Results

Based on patient numbers of outpatient care, the prevalence per 100,000 among males was 1,483.7 patients (1.5%), among females 2,905.5 (2.9%), in total 2,226.2 patients (2.2%). The age-standardised prevalence was 1,734.8 (1.7%) for males and 2,594.8 (2.6%) for females per 100,000 population, for a total of 2,237.6 (2.2%). The prevalence per 100,000 population was higher for women in all age groups. In age group 30–39, 40–49, 50–59, 60–69 and 70 + the overall prevalence was 0.2%, 0.8%, 2.7%, 5.0% and 7.7%, respectively, describing a continuously increasing trend. In 2018, the NHIFA spent 42.31 million EUR on the treatment of hip osteoarthritis. Hip osteoarthritis accounts for 1% of total nationwide health insurance expenditures. 36.8% of costs were attributed to the treatment of male patients, and 63.2% to female patients. Acute inpatient care, outpatient care and chronic and rehabilitation inpatient care were the main cost drivers, accounting for 62.7%, 14.6% and 8.2% of the total health care expenditure for men, and 51.0%, 20.0% and 11.2% for women, respectively. The average annual treatment cost per patient was 3,627 EUR for men and 4,194 EUR for women.

Conclusions

The prevalence of hip osteoarthritis was 1.96 times higher (the age-standardised prevalence was 1.5 times higher) in women compared to men. Acute inpatient care was the major cost driver in the treatment of hip osteoarthritis. The average annual treatment cost per patient was 15.6% higher for women compared to men.
Enhancing oral squamous cell carcinoma detection: a novel approach using improved EfficientNet architecture
Authors: Soni Aradhana , Sethy Prabira Kumar , Dewangan Amit Kumar , Nanthaamornphong Aziz , Behera Santi Kumari , Devi Baishnu
Published: May 2024

Problem

Oral squamous cell carcinoma (OSCC) is the eighth most prevalent cancer globally, leading to the loss of structural integrity within the oral cavity layers and membranes. Despite its high prevalence, early diagnosis is crucial for effective treatment.

Aim

This study aimed to utilize recent advancements in deep learning for medical image classification to automate the early diagnosis of oral histopathology images, thereby facilitating prompt and accurate detection of oral cancer.

Methods

A deep learning convolutional neural network (CNN) model categorizes benign and malignant oral biopsy histopathological images. By leveraging 17 pretrained DL-CNN models, a two-step statistical analysis identified the pretrained EfficientNetB0 model as the most superior. Further enhancement of EfficientNetB0 was achieved by incorporating a dual attention network (DAN) into the model architecture.

Results

The improved EfficientNetB0 model demonstrated impressive performance metrics, including an accuracy of 91.1%, sensitivity of 92.2%, specificity of 91.0%, precision of 91.3%, false-positive rate (FPR) of 1.12%, F1 score of 92.3%, Matthews correlation coefficient (MCC) of 90.1%, kappa of 88.8%, and computational time of 66.41%. Notably, this model surpasses the performance of state-of-the-art approaches in the field.

Conclusion

Integrating deep learning techniques, specifically the enhanced EfficientNetB0 model with DAN, shows promising results for the automated early diagnosis of oral cancer through oral histopathology image analysis. This advancement has significant potential for improving the efficacy of oral cancer treatment strategies.
Insights into pelvic insufficiency fracture following pelvic radiotherapy for cervical cancer: a comparative review
Authors: Haque Munima , Hossen Md Sakib
Published: May 2024

Background

Radiotherapy (RT)-induced pelvic insufficiency fractures (PIF) are prevalent in patients with cervical cancer. Inconclusive studies on PIF after cervical irradiation create uncertainty. This review examined PIF after RT in cervical patients, including its pathobiology, likely locations of fractures, incidence, clinical symptoms, and predisposing factors. We further discussed study limitations and therapeutic possibilities of PIF.

Methods

The following online resources were searched for relevant articles: Google Scholar and PubMed. The keywords ‘pelvic insufficiency fractures’, ‘cervical carcinoma’ and ‘cervical cancer’, as well as ‘chemoradiotherapy’, ‘chemoradiation’, and ‘radiotherapy’, were some of the terms that were used during the search.

Results

Patients with PIF report pelvic pain after radiation treatment for cervical cancer; the incidence of PIF ranges from 1.7 to 45.2%. Evidence also supports that among all patients treated with pelvic radiation, those who experienced pelvic insufficiency fractures invariably had at least one sacral fracture, making it the most frequently fractured bone in the body. Menopausal status, weight, BMI, age, and treatments and diagnosis modalities can influence PIF during radiotherapy.

Conclusions

In conclusion, our comparative review of the literature highlights significant heterogeneity in various aspects of PIF following radiation for patients with cervical cancer. This diversity encompasses prevalence rates, associated risk factors, symptoms, severity, diagnosis methods, preventive interventions, and follow-up periods. Such diversity underscores the complexity of PIF in this population and emphasizes the critical need for further research to elucidate optimal management strategies and improve patient outcomes.
Association of heavy menstrual bleeding with cardiovascular disease in US female hospitalizations
Authors: Dubey Pallavi , Reddy Sireesha , Singh Vishwajeet , Yousif Abdelrehman , Dwivedi Alok Kumar
Published: May 2024

Background

Heavy menstrual bleeding (HMB) is a common menstrual disorder associated with multiple risk factors of cardiovascular disease (CVD) in women. In addition, HMB is often present with irregular menstruation (IM) which is a risk factor for CVD outcomes. However, the relationship between HMB and CVD outcomes is unexplored in the presence or absence of IM. We determined the association of HMB with multiple CVD outcomes using a nationally representative sample of female hospitalizations in the US.

Methods

All hospitalizations of females with HMB diagnosis and normal menstrual cycles from ages of 18 to 70 years were extracted from the National Inpatient Sample Database, 2017. The HMB was defined using the International Classification of Diseases (ICD)-10 for excessive and frequent menstruation bleeding and included any current or history of HMB diagnosis. Outcomes including major adverse cardiovascular events (MACE), coronary heart disease (CHD), stroke, heart failure (HF), atrial fibrillation (AF) or arrhythmia, myocardial infarction (MI), and diabetes (DM) were defined using ICD-10 codes. Adjusted logistic regression and prosperity scores-matched logistic regression analyses were conducted to summarize adjusted associations with an odds ratio (OR) and a 95% confidence interval (CI).

Results

Among 2,430,851 hospitalizations, HMB was observed in 7762 (0.68%) females with age ≤ 40 years and 11,164 (0.86%) females with age > 40 years. Among hospitalizations with age ≤ 40 years, HMB was significantly associated with increased odds of CVD outcomes including MACE (OR = 1.61; 95% CI: 1.25, 2.08), CHD (OR = 1.72; 95% CI: 1.10, 2.71), stroke (OR = 1.95; 95% CI: 1.12, 3.40), HF (OR = 1.53; 95% CI: 1.15, 2.03), and AF/arrhythmia (OR = 1.84; 95% CI: 1.34, 2.54). These associations were confirmed in multiple sensitivity analyses. In contrast, HMB was not robustly associated with CVD events among hospitalizations of women with age > 40 years. HMB without IM was strongly associated with DM, HF, AF, and MACE outcomes while HMB with IM was strongly associated with CHD and AF outcomes in hospitalizations of young women.

Conclusions

HMB is associated with CVD events among US hospitalizations of young women. A routine investigation and screening of menstrual disorders, especially HMB, is useful for CVD risk stratification and management in young women.
The effects of saline water consumption on sperm parameters, testicular histopathology, hormonal and antioxidants concentrations in Barki Rams
Authors: Mohamed Rasha S. , Mohamed Ragab H , Wehrend Axel , Tahoun Enas A. , Hussein Hassan A.
Published: May 2024

The study aimed to assess the effects of water salinity on the sperm parameters, levels of cortisol, LH, FSH, testosterone and antioxidants as well as the testes’ histopathology in Barki rams. Fifteen healthy Barki rams (1–1.5 years) were divided into three equal depending on the type of drinking water for nine months. The rams in the tap water group (TW, water that contained 350 ppm of total dissolved salts (TDS). Males in the high saline water group (HSW) were permitted to consume high saline water with 8,934 ppm TDS, whereas those in the second group were permitted to have moderately saline water (MSW, 4,557 ppm TDS). High salt concentration in drinking water had adverse effect on sperm viability, morphology and sperm cell concertation. Nitric oxide and malondialdehyde concentrations in blood were significantly higher in the MSW and HSW groups than in TW. There was a significant decrease in glutathione concentration as well as superoxide dismutase activity in TDS and HSW. Cortisol was most highly concentrated in the HSW, next in the MSW, and least in TW. The testosterone, LH, and FSH concentrations in the HSW and MSW groups were significantly lower than in TW. As the salt concentration in drinking water increases, damage to testicular tissue. The MSW group demonstrating vacuolation of lining epithelial cells with pyknotic nuclei in the epididymis and necrosis and desquamation of spermatogenic cells in seminiferous tubules while HSW group displaying desquamated necrotic cells and giant cell formation in the epididymis, as well as damage to some of the seminiferous tubules and showed congestion, vacuolation of spermatogenic epithelium of seminiferous tubules, and desquamated necrotic spermatogenic epithelium. In conclusion, the salinity of the water has detrimental impacts on the sperm morphology, viability and concentration, hormones and antioxidant levels in Barki rams.
Impact of pH modification of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus)
Authors: Ibrahim Ahmed , Abd-Elrasoul Mohamed A. A. , Sabra Mahmoud S.
Published: May 2024

Background

Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation.

Results

Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug’s bioavailability. The MIC90 of the most hazardous bacteria isolated from equines’ eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239–342 min) and aqueous humor (238–330 min) with the modified tobramycin solution.

Conclusions

Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys’ ophthalmic infections at a pH of 8.26, isotonic with the donkeys’ tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.
Improved pediatric ICU mortality prediction for respiratory diseases: machine learning and data subdivision insights
Authors: Prithula Johayra , Chowdhury Muhammad E. H. , Khan Muhammad Salman , Al-Ansari Khalid , Zughaier Susu M. , Islam Khandaker Reajul , Alqahtani Abdulrahman
Published: May 2024

The growing concern of pediatric mortality demands heightened preparedness in clinical settings, especially within intensive care units (ICUs). As respiratory-related admissions account for a substantial portion of pediatric illnesses, there is a pressing need to predict ICU mortality in these cases. This study based on data from 1188 patients, addresses this imperative using machine learning techniques and investigating different class balancing methods for pediatric ICU mortality prediction. This study employs the publicly accessible “Paediatric Intensive Care database” to train, validate, and test a machine learning model for predicting pediatric patient mortality. Features were ranked using three machine learning feature selection techniques, namely Random Forest, Extra Trees, and XGBoost, resulting in the selection of 16 critical features from a total of 105 features. Ten machine learning models and ensemble techniques are used to make accurate mortality predictions. To tackle the inherent class imbalance in the dataset, we applied a unique data partitioning technique to enhance the model's alignment with the data distribution. The CatBoost machine learning model achieved an area under the curve (AUC) of 72.22%, while the stacking ensemble model yielded an AUC of 60.59% for mortality prediction. The proposed subdivision technique, on the other hand, provides a significant improvement in performance metrics, with an AUC of 85.2% and an accuracy of 89.32%. These findings emphasize the potential of machine learning in enhancing pediatric mortality prediction and inform strategies for improved ICU readiness.
The behaviour of adult Anopheles gambiae, sub-Saharan Africa’s principal malaria vector, and its relevance to malaria control: a review
Authors: Takken Willem , Charlwood Derek , Lindsay Steve W.
Published: May 2024

Background

Mosquitoes of the Anopheles gambiae complex are one of the major vectors of malaria in sub-Saharan Africa. Their ability to transmit this disease of major public health importance is dependent on their abundance, biting behaviour, susceptibility and their ability to survive long enough to transmit malaria parasites. A deeper understanding of this behaviour can be exploited for improving vector surveillance and malaria control.

Findings

Adult mosquitoes emerge from aquatic habitats at dusk. After a 24 h teneral period, in which the cuticle hardens and the adult matures, they may disperse at random and search upwind for a mate or to feed. Mating generally takes place at dusk in swarms that form over species-specific ‘markers’. Well-nourished females may mate before blood-feeding, but the reverse is true for poorly-nourished insects. Females are monogamous and only mate once whilst males, that only feed on nectar, swarm nightly and can potentially mate up to four times. Females are able to locate hosts by following their carbon dioxide and odour gradients. When in close proximity to the host, visual cues, temperature and relative humidity are also used. Most blood-feeding occurs at night, indoors, with mosquitoes entering houses mainly through gaps between the roof and the walls. With the exception of the first feed, females are gonotrophically concordant and a blood meal gives rise to a complete egg batch. Egg development takes two or three days depending on temperature. Gravid females leave their resting sites at dusk. They are attracted by water gradients and volatile chemicals that provide a suitable aquatic habitat in which to lay their eggs.

Conclusion

Whilst traditional interventions, using insecticides, target mosquitoes indoors, additional protection can be achieved using spatial repellents outdoors, attractant traps or house modifications to prevent mosquito entry. Future research on the variability of species-specific behaviour, movement of mosquitoes across the landscape, the importance of light and vision, reproductive barriers to gene flow, male mosquito behaviour and evolutionary changes in mosquito behaviour could lead to an improvement in malaria surveillance and better methods of control reducing the current over-reliance on the indoor application of insecticides.
A thematic analysis of MDMA-related harm and harm reduction experiences and knowledge in Aotearoa New Zealand
Authors: Whelan Jai , Ward Ryan D. , Noller Geoff
Published: May 2024

Background

Methylenedioxymethamphetamine (MDMA) is a popular drug worldwide and use is prevalent in Aotearoa New Zealand. Although associated with some significant harms, including fatalities, MDMA is ultimately less harmful than other commonly consumed drugs. We aimed to expand the understanding of MDMA harm and harm reduction strategies from a consumer perspective so that national harm reduction efforts can be better informed.

Methods

We conducted 14 semi-structured focus group discussions including 60 people (aged 18–67, median = 21) who use MDMA in the Southern region of Aotearoa New Zealand to explore their thoughts and experiences regarding MDMA associated harm and harm reduction. Reflexive thematic analysis was conducted from a critical realist perspective.

Results

Five themes were generated; (1) Mindset and setting matters; (2) Looking after your body and mind, not overdoing it; (3) Other substances increase risk and harm; (4) Trusted friends and peers are protective; and (5) Valid information is key for healthy self-determination; and one subtheme 5.1) Drug checking is essential harm reduction.

Conclusions

We discuss the implications for MDMA consumers and aim to inform national drug policy and the harm reduction practices of consumers and organisations, for the ultimate purpose of reducing MDMA-related harm in Aotearoa New Zealand.
Differences between the intestinal microbial communities of healthy dogs from plateau and those of plateau dogs infected with Echinococcus
Authors: Liu Jia , Jiang Xiaojie , Lei Wen , Xi Yuan , Zhang Qing , Cai Huixia , Ma Xiao , Liu Yufang , Wang Wei , Liu Na , Zhang Xiongying , Ma Wanli , Zhao Cunzhe , Ni Bin , Zhang Wen , Wang Yongshun
Published: May 2024

Objective

Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics.

Methods

In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract.

Results

Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families.

Conclusion

The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.
Local Application of Tanshinone IIA protects mesenchymal stem cells from apoptosis and promotes fracture healing in ovariectomized mice
Authors: Cheng Shao , Hu Xiaohui , Sun Kanghui , Huang Ziyu , Zhao Yongjian , Sun Yueli , Zeng Bo , Wang Jing , Zhao Dongfeng , Lu Sheng , Shi Qi , Wang Yongjun , Zhang Weian , Liu Xinhua , Shu Bing
Published: May 2024

Background

Elderly patients suffering from osteoporotic fractures are more susceptible to delayed union or nonunion, and their bodies then are in a state of low-grade chronic inflammation with decreased antioxidant capacity. Tanshinone IIA is widely used in treating cardiovascular and cerebrovascular diseases in China and has anti-inflammatory and antioxidant effects. We aimed to observe the antioxidant effects of Tanshinone IIA on mesenchymal stem cells (MSCs), which play important roles in bone repair, and the effects of local application of Tanshinone IIA using an injectable biodegradable hydrogel on osteoporotic fracture healing.

Methods

MSCs were pretreated with or without different concentrations of Tanshinone IIA followed by H2O2 treatment. Ovariectomized (OVX) C57BL/6 mice received a mid-shaft transverse osteotomy fracture on the left tibia, and Tanshinone IIA was applied to the fracture site using an injectable hydrogel.

Results

Tanshinone IIA pretreatment promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes, and inhibited H2O2-induced reactive oxygen species accumulation in MSCs. Furthermore, Tanshinone IIA reversed H2O2-induced apoptosis and decrease in osteogenic differentiation in MSCs. After 4 weeks of treatment with Tanshinone IIA in OVX mice, the bone mineral density of the callus was significantly increased and the biomechanical properties of the healed tibias were improved. Cell apoptosis was decreased and Nrf2 expression was increased in the early stage of callus formation.

Conclusions

Taken together, these results indicate that Tanshinone IIA can activate antioxidant enzymes to protect MSCs from H2O2-induced cell apoptosis and osteogenic differentiation inhibition. Local application of Tanshinone IIA accelerates fracture healing in ovariectomized mice.
Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer
Authors: Xu Wenjing , Li Yingqiu , Liu Lumei , Xie Jing , Hu Zongren , Kuang Shida , Fu Xinying , Li Bonan , Sun Tiansong , Zhu Congxu , He Qinghu , Sheng Wen
Published: May 2024

Background

Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa.

Methods

A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development.

Results

After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2.

Conclusions

ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.
Local intralesional talimogene laherparepvec therapy with complete local response in oral palatine mucosal melanoma: a case report
Authors: Chitnis Saurabh D. , Seim Nolan B. , Kendra Kari
Published: May 2024

Background

Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec’s initial phase III clinical trial.

Case presentation

We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where—based on the patient’s complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases—local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas.

Conclusion

The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment.
Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial
Authors: Harris Violaine K. , Stark James , Williams Armistead , Roche Morgan , Malin Michaela , Kumar Anjali , Carlson Alyssa L. , Kizilbash Cara , Wollowitz Jaina , Andy Caroline , Gerber Linda M. , Sadiq Saud A.
Published: May 2024

Background

Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS.

Methods

The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement.

Results

Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and − 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and − 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment.

Conclusion

Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients.

Trial Registration

ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1.
Nonexistence results for a time-fractional biharmonic diffusion equation
Authors: Jleli Mohamed , Samet Bessem
Published: May 2024

We consider weak solutions of the nonlinear time-fractional biharmonic diffusion equation $\partial _{t}^{\alpha }u+\partial _{t}^{\beta }u+u_{xxxx}=h(t,x)|u|^{p}$

∂
t
α

u
+

∂
t
β

u
+

u

x
x
x
x

=
h
(
t
,
x
)

|
u
|

p

in $(0,\infty )\times (0,1)$
(
0
,
∞
)
×
(
0
,
1
)
subject to the initial conditions $u(0,x)=u_{0}(x)$
u
(
0
,
x
)
=

u
0

(
x
)
, $u_{t}(0,x)=u_{1}(x)$

u
t

(
0
,
x
)
=

u
1

(
x
)
and the Navier boundary conditions $u(t,1)=u_{xx}(t,1)=0$
u
(
t
,
1
)
=

u

x
x

(
t
,
1
)
=
0
, where $\alpha \in (0,1)$
α
∈
(
0
,
1
)
, $\beta \in (1,2)$
β
∈
(
1
,
2
)
, $\partial _{t}^{\alpha}$

∂
t
α

(resp. $\partial _{t}^{\beta}$

∂
t
β

) is the fractional derivative of order α (resp. β) with respect to the time-variable in the Caputo sense, $p>1$
p
>
1
and h is a measurable positive weight function. Using nonlinear capacity estimates specifically adapted to the fourth-order differential operator $\frac{\partial ^{4}}{\partial x^{4}}$

∂
4

∂

x
4

, the domain, the initial conditions and the boundary condition, a general nonexistence result is established. Next, some special cases of weight functions h are discussed.
Preoperative rectus femoris muscle ultrasound, its relationship with frailty scores, and the ability to predict recovery after cardiac surgery: a prospective cohort study
Authors: Yau Derek King Wai , Griffith James Francis , Underwood Malcolm John , Joynt Gavin Matthew , Lee Anna
Published: May 2024

Background

Frailty is common in patients undergoing cardiac surgery and is associated with poorer postoperative outcomes. Ultrasound examination of skeletal muscle morphology may serve as an objective assessment tool as lean muscle mass reduction is a key feature of frailty.

Methods

This study investigated the association of ultrasound-derived muscle thickness, cross-sectional area, and echogenicity of the rectus femoris muscle (RFM) with preoperative frailty and predicted subsequent poor recovery after surgery. Eighty-five patients received preoperative RFM ultrasound examination and frailty-related assessments: Clinical Frailty Scale (CFS) and 5-m gait speed test (GST5m). Association of each ultrasound measurement with frailty assessments was examined. Area under receiver-operating characteristic curve (AUROC) was used to assess the discriminative ability of each ultrasound measurement to predict days at home within 30 days of surgery (DAH30).

Results

By CFS and GST5m criteria, 13% and 34% respectively of participants were frail. RFM cross-sectional area alone demonstrated moderate predictive association for frailty by CFS criterion (AUROC: 0.76, 95% CI: 0.66–0.85). Specificity improved to 98.7% (95% CI: 93.6%-100.0%) by utilising RFM cross-sectional area as an ‘add-on’ test to a positive gait speed test, and thus a combined muscle size and function test demonstrated higher predictive performance (positive likelihood ratio: 40.4, 95% CI: 5.3–304.3) for frailty by CFS criterion than either test alone (p < 0.001). The combined ‘add-on’ test predictive performance for DAH30 (AUROC: 0.90, 95% CI: 0.81–0.95) may also be superior to either CFS or gait speed test alone.

Conclusions

Preoperative RFM ultrasound examination, especially when integrated with the gait speed test, may be useful to identify patients at high risk of frailty and those with poor outcomes after cardiac surgery.

Trial registration

The study was registered on the Chinese Clinical Trials Registry (ChiCTR2000031098) on 22 March 2020.
Quality of health care for patients with coronary heart disease and comorbid mental disorders: a prospective cohort study
Authors: Nordmeyer Laura , Leikert Charlotte , Sannemann Lena , Keller Kai , Leminski Christin , Meixner Adriana , Peltzer Samia , Werner Belinda , Kuntz Ludwig , Pfaff Holger , Schulz-Nieswandt Frank , Jessen Frank , Albus Christian ,   Cologne Research and Development Network (CoRe-Net) Study Group, Meyer Ingo , Scholten Nadine , Stock Stephanie , Strupp Julia , Voltz Raymond
Published: May 2024

Background

Coronary heart disease (CHD) is often associated with mental disorders (MDs). Comorbid MDs reduce the quality of life and increase cardiac morbidity and mortality. Nevertheless, there is little and inconsistent research on the management of MDs in CHD patients. To bridge this gap, this study aims to gain insight into the long-term course of MD-related health care for patients with CHD, in order to identify opportunities for care improvement.

Methods

In this prospective cohort study, we investigated whether CHD patients with or without expert-rated MD at baseline (N = 364) received different MD-related health care from either their general practitioner (GP) or cardiologist at follow-up, M = 2.7 [2.0–4.0] years later. In the follow-up assessment, N = 131 CHD patients participated and received questionnaires capturing sociodemographic, mental health, and MD-related health care characteristics. Descriptive statistics, t-tests and chi-squared tests were used for analyses.

Results

We found significant differences in MD-related health care. CHD patients with MD were more likely to be examined psychologically/psychiatrically (MD 55.9%, non-MD 16.7%, p = < .001) and diagnosed with MD (MD 55.9%, non-MD 13.5%, p = .020) by their GP or cardiologist. Recommendations for and responses to requests for psychotherapy were more likely in MD patients compared to non-MD patients (MD 38.7%, non-MD 11.8%, p = .012 and MD 38.5%, non-MD 11.8%, p = .031, respectively). No significant differences were found concerning physicians’ active demand for patients’ mental health, referral to a specialist for additional diagnostics, provision of information about the diagnosed MD and further treatment options, response to the patients’ request for psychopharmacotherapy, help received in finding psychotherapy or psychopharmacotherapy, and actual receipt of these treatments.

Conclusions

The results indicate differences in MD-related health care of CHD patients with and without comorbid MD. However, they still highlight the need to further encourage primary care physicians treating CHD to adequately address MDs, provide further diagnostics, support, and information to affected patients. To address this, physicians may benefit from awareness training on the association between CHD and MDs and on appropriate communication with MD patients.

Trial registration

German clinical trials register (Deutsches Register Klinischer Studien, DRKS) Registration Number: ID DRKS00022154, date of registration: 02.11.2021.
Autonomous precision resuscitation during ground and air transport of an animal hemorrhagic shock model
Authors: Pinsky Michael R. , Gomez Hernando , Guyette Francis X. , Weiss Leonard , Dubrawski Artur , Leonard Jim , MacLachlan Robert , Gordon Lisa , Lagattuta Theodore , Salcido David , Poropatich Ronald
Published: May 2024

We tested the ability of a physiologically driven minimally invasive closed-loop algorithm, called Resuscitation based on Functional Hemodynamic Monitoring (ReFit), to stabilize for up to 3 h a porcine model of noncompressible hemorrhage induced by severe liver injury and do so during both ground and air transport. Twelve animals were resuscitated using ReFit to drive fluid and vasopressor infusion to a mean arterial pressure (MAP) > 60 mmHg and heart rate < 110 min−130 min after MAP < 40 mmHg following liver injury. ReFit was initially validated in 8 animals in the laboratory, then in 4 animals during air (23nm and 35nm) and ground (9 mi) to air (9.5nm and 83m) transport returning to the laboratory. The ReFit algorithm kept all animals stable for ~ 3 h. Thus, ReFit algorithm can diagnose and treat ongoing hemorrhagic shock independent to the site of care or during transport. These results have implications for treatment of critically ill patients in remote, austere and contested environments and during transport to a higher level of care.
Competition between biodetoxification fungus and lactic acid bacterium in the biorefinery processing chain for production of cellulosic L-lactic acid
Authors: Li Zhibin , Zhang Lingxiao , He Niling , Zhang Bin , Bao Jie
Published: May 2024

Biodetoxification fungus selectively degrades toxic inhibitors generated from pretreatment of lignocellulose without consuming fermentable sugars. However, one barrier for practical application is the sustained cell viability in the consequent fermentation step to compete the fermentable sugars with fermenting strains, resulting in sugar loss and reduced target product yield. This study investigated the competitive growth property between the biodetoxification fungus Paecilomyces variotii FN89 and the L-lactic acid bacterium Pediococcus acidilactici ZY271 under varying temperature and lactic acid osmatic stress. The results show that the L-lactic acid bacterium Ped. acidilactici ZY271 showed less thermotolerance to Pae. variotii FN89 at high temperature of 45 °C to 50 °C in both synthetic medium and wheat straw hydrolysate. In the higher temperature environment, the growth of the biodetoxification strian failed to compete with the lactic acid fermentation strain and was quickly eliminated from the fermentation system. The high temperature fermentation facilitated a fast transition from the detoxification stage to the fermentation stage for higher production of L-lactic acid.
Near vision in patients with DME and RVO treated with aflibercept and correlation with NEI VFQ-25 questionnaire
Authors: Sulavikova Zuzana Anwarzai , Sustykevicova Zuzana , Kacerik Marek , Krasnik Vladimir
Published: May 2024

Background

The aim of this study is to evaluate near and distance visual acuity (VA) and their correlation with the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) outcomes in patients with diabetic macular edema (DME) and macular edema due to retinal vein occlusion (RVO) treated with aflibercept.

Methods

In this prospective study, we included 87 eyes of patients diagnosed with DME (n = 61) and RVO (n = 26), who received aflibercept treatment and were followed until the 8th injection. Near VA was examined on the 1st, 2nd, 3rd, 4th, 6th, and 8th injection, and patients completed the NEI VFQ-25 on the 1st, 4th, and 8th aflibercept injection.

Results

The mean near VA at baseline in all eyes was 0.89 ± 0.12 logMAR. With every administration, there was a statistically significant improvement; on the 4th (0.70 ± 0.19; p = 0.000) and the 8th application (0.60 ± 0.19; p = 0.000). At baseline, the mean NEI VFQ-25 total score was 71 ± 14%, and improved to 81 ± 13% (p = 0.000) on the 8th injection. The most significant score gain was recorded in the near VA subscale (+ 20 ± 14%, p = 0.000). There was no statistically significant difference between DME and RVO group in the questionnaire or near VA outcomes.

Conclusion

Aflibercept treatment resulted in a remarkable improvement of near vision by 4 lines of logMAR optotype after the 8th application. The near vision questionnaire subscale, initially scoring the lowest, exhibited the greatest gain during the treatment period. This underscores the importance of near vision and reading ability for patients with DME and RVO.
A scoping review on how generative artificial intelligence transforms assessment in higher education
Authors: Xia Qi , Weng Xiaojing , Ouyang Fan , Lin Tzung Jin , Chiu Thomas K.F.
Published: May 2024

Generative artificial intelligence provides both opportunities and challenges for higher education. Existing literature has not properly investigated how this technology would impact assessment in higher education. This scoping review took a forward-thinking approach to investigate how generative artificial intelligence transforms assessment in higher education. We used the PRISMA extension for scoping reviews to select articles for review and report the results. In the screening, we retrieved 969 articles and selected 32 empirical studies for analysis. Most of the articles were published in 2023. We used three levels—students, teachers, and institutions—to analyses the articles. Our results suggested that assessment should be transformed to cultivate students’ self-regulated learning skills, responsible learning, and integrity. To successfully transform assessment in higher education, the review suggested that (i) teacher professional development activities for assessment, AI, and digital literacy should be provided, (ii) teachers’ beliefs about human and AI assessment should be strengthened, and (iii) teachers should be innovative and holistic in their teaching to reflect the assessment transformation. Educational institutions are recommended to review and rethink their assessment policies, as well as provide more inter-disciplinary programs and teaching.
The outcomes and complications of percutaneous interventions in chronic total coronary occlusion
Authors: Suleman Muhammad , Arif Nayyar , Khan Muhammad Ishaq , Jibran Muhammad Saad , Jamil Muhammad , Khan Shafi Ullah , Khan Shah Sawar , Maken Ghulam Rasool
Published: May 2024

Background

The limited availability of complex coronary intervention facilities and qualified operators, due to the high cost associated with chronic total occlusion (CTO) percutaneous intervention (PCI) equipment and a shortage of necessary skills, has led to a scarcity of capable medical centers in Pakistan. This study seeks to examine the outcomes and potential complications associated with CTO PCI procedures conducted at the Cardiac Catheterization Laboratories of a prominent national institute in Pakistan, which handles a large volume of cases.

Results

Three hundred and six patients were included in the study in the study period of six months. The mean age was 59.49 (± 9.16) years: 256 (83.66%) were male and 50 (16.34%) were female. CTO was successfully re-vascularized in 237 (77.5%) with a complication rate of 13.7%. Two hundred and ninety-eight (97.39%) patients underwent an antegrade approach, while RCA was the most common target vessel (47.71%). Diabetes was the only significant associated risk factor with CTO PCI failure (30.43% vs. 30.43%, P-value = 0.015).

Conclusion

We achieved an excellent procedural success rate with a low complication rate. CTO procedural failure is associated with a higher complication rate, and diabetes is among the risk factors that lead to higher procedural failure.
Predictors of suicidal behaviors among school-going adolescents: a cross sectional study in Indonesia
Authors: Kurniawan Dedi , Fitriawan Akbar Satria , Susanti Brigitta Ayu Dwi , Firdaus Insanul , Suparmanto Gatot , Kafil Raisa Farida , Wulandari Apri Nur , Setyaningsih Wiwit Ananda Wahyu , Puspitarini Zenni , Wijoyo Eriyono Budi
Published: May 2024

Background

Adolescents are a high-risk age group for committing suicide, and the risk substantially increases from early to late adolescence. Adolescence also serves as critical time period for early detection and intervention to prevent suicidal behaviors. This study aimed to assess the prevalence of suicidality and identify significant predictors of suicidality among adolescents.

Methods

A cross-sectional observational study was conducted between January-December 2023. Adolescents aged 14–18 years old (n = 2317) were consecutively recruited from 15 high schools across four provinces on Java Island in Indonesia. Self-reported validated instruments in Indonesian were used to assess sociodemographic profiles, self-esteem (RSES), hopelessness (BHS), loneliness (ULS-3), perceived social support (MSPSS), depression (PHQ-9), resilience (CD-RISC-10), suicidality (SBQ-R). With adjusted odds ratio (AOR) and 95% confidence interval (CI), binary logistic regression analysis was used to determine significant predictors of suicidality.

Results

The prevalence of lifetime suicide ideation was 26.5%, lifetime suicide plans were 18.2%, lifetime suicide threat was 14.1%, and lifetime suicide attempt was 4.4%. The prevalence of 12-month suicide ideation was 43.1%. The following variables were identified and significantly associated with suicidality (p < 0.05): female students (AOR = 1.912; 95%CI:1.507–2.425), chronic illness (AOR = 2.886; 95%CI:1.545–5.389), low resilience (AOR = 1.347; 95%CI:1.036–1.750), low self-esteem (AOR = 2.020; 95%CI:1.578–2.585), low family support (AOR = 3.532; 95%CI:2.486–5.017), loneliness (AOR = 1.611; 95%CI:1.211–2.143), depression (AOR = 4.882; 95%CI = 3.861–6.175), and hopelessness (AOR = 1.602; 95%CI:1.154–2.224). Nagelkerke R square was 0.364 indicating the regression model explained 36.4% of variance in suicidality.

Conclusions

Our study revealed several significant predictors of suicidality among adolescents which can be targeted to develop suicide prevention strategies.