bluuebunny/crossref_metadata_2025 huggingface dataset:
“I’m scared of the nurses telling other people I am a transwoman”: Disclosure and nondisclosure of gender identity among trans women in Ghana’s urban slums– BSGH010
Authors: Shamrock Osman Wumpini , Dakpui Henry Delali , Agbemedu George Rudolph Kofi , Boyd Donte T , Islam Kharul , Mashoud Ibrahim Wunpini , Zigah Edem Yaw , Ababio Michael Nti , Charles Nukunu , Guure Chris , Nelson LaRon E. , Abu-Ba’are Gamji Rabiu
Published: April 2024

Background: Trans women in Ghana and SSA face dilemmas regarding the disclosureof their gender identities due to potential discrimination they may face during visits to health facilities. This study investigates the experiences of trans women living in urban slums in Ghana and explores factors influencing their decisions to disclose or withhold their gender identities while seeking healthcare.
Design: We used purposive and snowball sampling techniques to recruit 20 trans women from slums in Ghana’s Greater Accra Metropolitan Area and conducted in-depth qualitative interviews to gather data. Data was analyzed using Nvivo and coded to arrive at our results.
Results: Our study revealed four reasons why trans women concealed their gender identities when seeking healthcare: (a) Gossiping among healthcare professionals, (b) Rude and unwelcoming gestures from health workers, (c) Avoidance of probing questions from health workers, and (d) Delayed treatment and unsatisfactory services by health professionals. The study also found two reasons for trans women to disclose their gender identity while seeking healthcare: (a) LGBTQ-friendly facilities as a reason for disclosure and (b) Intrusive questioning.
Conclusion: These findings contribute to the experiences of trans women living in deprived communities such as urban slums, contributing to the existing literature on challenges associated with the disclosure and nondisclosure of gender identity when accessing healthcare in these communities. Additionally, our results underscore the urgent need for reevaluating health policies and implementing targeted training and practices for healthcare professionals dealing with trans women in Ghana.
A novel fluorescent probe for nitroreductase detection and imaging of cancer cells under hypoxia conditions
Authors: Sun Tong , Wu Lei , Cui Mengyuan , Zhao Guisen
Published: April 2024

Nitroreductase (NTR) is to be pivotal in the biodegradation of nitroaromatics. NTR is produced in tumor tissues under hypoxic conditions, which is one of the markers for early tumor diagnosis. In this study, a novel probe FD-NTR was developed for NTR detection. Probe FD-NTR can exhibit a specific reaction with NTR in the presence of NADH. The probe displayed satisfactory selectivity and sensitivity towards NTR, with a calculated limit of detection of 12 ng/mL. Under the conditions of low cytotoxic hypoxia, the FD-NTR probe has shown successful application in imaging both MCF-7 cells and tumor tissues, which indicated that the FD-NTR probe holds promising application prospects for detecting NTR in tumors.
Fractal evolution characteristics of fracture meso-damage in uniaxial compression rock masses using bonded block model
Authors: Lan Ming , He Yan , Wang Chunlong , Liu Xingquan , Ren Guoqing , Zhang Shuwen
Published: April 2024

In the realm of underground mining engineering, an investigation into the failure mode of deep fractured rock masses and their corresponding acoustic emission signal characteristics is conducted via uniaxial compression tests. Subsequently, a fractal damage renormalization group mechanical model is formulated to elucidate the behavior of such fractured rock masses. Employing the BBM numerical simulation method, the fracture process of synthetic rock samples is analyzed, thereby confirming the efficacy of the aforementioned mechanical model. The numerical simulations underscore that the expansion of fractures fundamentally underpins the deterioration of rock mass strength. A decrease in peak load correlates with an increase in fracture fractal dimension, resulting in a 14.2% reduction in compressive strength alongside an approximate 8.7% rise in average fracture fractal dimension. Comparison between tetrahedral and Voronoi block synthetic rock samples reveals the former's superior aptitude in depicting the fracture behavior of fractured rock masses, particularly in terms of simulating acoustic emission characteristics and failure modes. Moreover, the variation in fracture fractal dimension with the hole defect's position is observed, with its maximum value aligning with the vertical hole defect axis. This observation underscores the potential utility of visually monitoring deep rock fracture dynamics as a foundational element for quantitatively evaluating fracture damage and strength degradation in deep rock formations.
The combined effects of electrolyte addition and mechanical shearing on cellulose nanocrystal alignment
Authors: Ghosh Ananya , Amita Sadat Kamal , Davis Virginia , Jiang Zhihua
Published: April 2024

This research investigated the combined effects of electrolyte addition and mechanical shearing on the alignment, optical properties, and rheological characteristics of cellulose nanocrystal (CNC) films. Changes in aqueous CNC gels’ rheological properties due to electrolyte addition were correlated to the properties of the dried films. The alignment in dried CNC films was measured using the order parameter computed by UV-Vis transmission spectroscopy and qualitatively through cross-polarized optical microscopy. In the absence of electrolytes, a single stroke of mechanical shearing at a shear rate of 100 s-1 is insufficient to significantly align CNC in CNC gel. However, the addition of electrolytes improves the alignment of CNC, resulting in an increase of order parameters, such as from 0.31 to 0.88 for NaCl addition, even at a lower shear rate of 20s-1. This work shows the addition of electrolytes combined with mechanical shearing is a more effective approach to tuning CNC alignment to produce transparent and less hazy CNC films from CNC gel.
Causal inference study on the influence of anemia indicators on the incidence of allergic rhinitis: two- sample Mendelian randomization
Authors: Chen YanNi , ChenFei Song , HaiDong Yu , Tao Liu , XinMin Han
Published: April 2024

Anemia and allergic rhinitis (AR) are prevalent clinical conditions in children. Previous studies have suggested an association between anemia and AR. Using Mendelian randomization (MR) analysis, we investigated causality with regard to the influence of anemia indicators on the incidence of AR. We searched the IEU OpenGWAS database for summary information on genome-wide association studies (GWAS) of anemia and AR in European populations. Three methods, MR-Egger, weighted median (WM), and inverse variance weighted (IVW), were utilized to evaluate the causal link between SLE and thyroid disease. We assessed pleiotropy and heterogeneity using MR-Egger intercept, MR-PRESSO, and Cochran’s Q test, among others. The IVW model revealed a significant causal association between anemia and AR. As the severity of anemia increased (OR = 1.02, p < 0.05), the risk of AR also increased. Moderate heterogeneity was observed (Cochran’s Q p-value < 0.05; 25% > I2 > 50%) among significant anemia-associated indicators in the MR results of AR (IVW). The MR-Egger regression was used to assess the horizontal pleiotropy of the instrumental variables. The statistical hypothesis test P-values of the intercept terms of each index exceeded 0.05, and the intercept was close to zero, indicating that the causal inference in this study was unaffected by horizontal pleiotropy. The MR analysis results support a potential causal link between anemia and AR, suggesting that anemia is a risk factor for AR. These insights could contribute towards raising awareness regarding the pathogenesis of AR and aid the formulation of strategies for its prevention, treatment, and prognosis.
Comparative Evaluation of Closed Versus Open Reduction Techniques in Straddle Fractures: A Retrospective Analysis of 69 Patients
Authors: Yu Yi-Hsun , Lai Chih-Yang , Chen I-Jung , Hsu Yung-Heng , Chou Ying-Chao
Published: April 2024

Background
Osteosynthesis techniques for addressing straddle fractures include closed reduction and fixation (CRF) and open reduction and fixation (ORF). Although CRF offers the advantage of being a minimally invasive surgery, ORF ensures precise reduction and secure fixation. The optimal surgical approach, whether employing CRF or ORF, to achieve superior osteosynthesis outcomes remains uncertain. This study aimed to compare the perioperative characteristics of the two methods and identify an optimal treatment approach tailored to each clinical indication.
Methods
We performed a retrospective analysis of patients with pelvic ring injuries at a single trauma center admitted between 2016 and 2021. Among this cohort, 69 patients with straddle fractures, with or without posterior pelvic ring injuries, were identified. The patients were categorized into two groups based on the treatment protocol: the CRF and ORF groups. Preoperative conditions, intraoperative features, and radiological outcomes were systematically compared and analyzed.
Results
A total of 69 patients with 138 superior pubic rami fractures underwent surgical treatment using either closed (57 superior pubic rami) or open (81 superior pubic rami) methods. Application of CRF significantly prevented fractures in Nakatani zone I (P = 0.003). ORF was employed for segmental fractures of the pubic ramus (P = 0.03) and fractures with greater displacement in the axial plane (P = 0.03). Additionally, ORF resulted in a more symmetric pelvic reduction according to the Lefaivre criteria (P = 0.003).
Conclusion
Both CRF and ORF demonstrated the ability to achieve satisfactory radiological outcomes in straddle fractures. The use of an established treatment protocol can assist surgeons in making informed decisions regarding the optimal treatment approach.
Level of Evidence
Therapeutic III
Prevalence of Intestinal Parasitic Helminthes, the Neglected Tropical Diseases, and Its Associated Risk Factors in Mekaneselam Town, South Wollo, Ethiopia
Authors: Wondimagegn Moges Kibret , Hailu Lulit Tegegne
Published: April 2024

Background
Intestinal parasitic (IP) infections caused by helminthes are among the most significant public health concerns that mainly affect deprived people in Sub-Sahara African countries. The aim of this study was to assess the prevalence and associated risk factors of intestinal parasitic helminthes among patients attending Mekaneselam hospital.
Method
In this cross-sectional study stool specimens were collected and examined microscopically to detect intestinal helminthes using direct wet-mount and formal-ether concentration techniques. A structured questionnaire was employed to obtain information regarding the socio-demographic characteristics and associated risk factors. Data was analyzed using SPSS version 25.
Result
The overall prevalence of the parasitic helminthes was 12.6% in Mekaneselam town. Seven intestinal helminthe species namely Ascaris lumbricoides (5.6%), Trichuris trichiura (2.2%), Enterobius vermicularis (1.7%), hookworm species (1.2%), Hymenolepsis nana (1.0%), Schistosoma mansoni (0.2%) and Tania species with a prevalence rate of (0.2%) were identified. Significant positive associations observed between intestinal helminthes infection and the socio-demographic characteristics including marital status (χ2 = 7.97, p = 0.047), educational level (χ2 = 9.34, p = 0.025) and residence (χ2 = 3.90, p = 0.048). The odds of being infected with IP helminthes in those divorced patients were three times more than those who were married (AOR = 3.21, CI = 1.15–8.96, p = 0.03). Regarding the education level, illiterate were four times (AOR = 2.61, CI = 1.24–5.49, p = 0.011) and those who attended primary school were three times (AOR = 2.3, CI = 1.029–5.143, p = 0.042), more likely to have helminthic infection. Participants who did not wash their hands after toilet were five times more likely to acquire IP helminthes than their counterparts (AOR = 4.36, CI = 2.83–6.72, p = 0.000). In the case of the feeding habit, study subjects who ate unwashed vegetables were more likely to acquire helminthes than those who did not eat unwashed vegetables (AOR = 5. 43, CI = 4.33–23.77, p = 0.000).
Conclusion
This study showed considerable prevalence of intestinal helminthes infections in the study area that deserve attentions from concerned bodies.
Population genetic structure of the European pond turtle (Emys orbicularis) at the northern edge of the Pannonian Basin
Authors: Mikulíček Peter , Papežík Petr , Danko Stanislav , Dankovics Róbert , Gruľa Daniel , Halpern Bálint , Havaš Peter , Heltai Botond , Horváth Enikő , Kušík Tomáš , Puchala Peter , Schindler Maria , Vongrej Viliam , Uhrin Marcel
Published: April 2024

Populations of plants and animals at the edge of a species’ range may exhibit lower genetic diversity due to a combination of historical (e.g., postglacial dispersal) and contemporary (e.g., lower effective population size, stronger genetic drift, bottlenecks, and others) processes. In this study, we analysed the genetic structure of populations of the European pond turtle (Emys orbicularis) in the northern part of the Pannonian Basin (Slovakia, Hungary, Austria), which represents the edge of the species’ range. Using mtDNA and microsatellite markers, we aimed to assign individuals and populations into phylogeographic lineages and to determine genetic variation and population structure. Our study revealed that most individuals from natural populations belong to mtDNA lineage II (widely distributed haplotype IIa, and likely endemic haplotypes IIl and II-Marcelová), which is typical for the whole Pannonian region. However, non-native haplotypes were detected in one Slovak population (haplotype Ib) and in the Austrian Donau Auen National Park (haplotype IVa). Microsatellite markers revealed high variability comparable to that in other parts of the range, suggesting that marginal populations may not necessarily have reduced genetic diversity. A genetically mixed population was found in the Donau Auen National Park, consisting of turtles belonging to mtDNA lineage II (taxonomically assessed as subspecies E. orbicularis orbicularis) and lineage IV (taxonomically assessed as E. orbicularis hellenica), which is native to the circum-Adriatic region. The admixture suggests intense hybridization and introgression between the two lineages (subspecies).
Feasibility and Acceptability of a Mobile Health Application Among Adolescents and Young Adults Living with HIV in Fako Division, South West, Cameroon: Guidance for Development
Authors: Njumkeng Charles , Nicholas Tendongfor , Mvilongo Prudence Tatiana Nti , Tanue Elvis A. , Amin Elvis T. , Abang Louis , Egbe Thomas Obinchemti , Njukeng Patrick A.
Published: April 2024

Mobile health applications have emerged as promising tools for improving healthcare delivery and patient outcomes, particularly in the context of HIV care. Adolescents and young adults living with HIV face unique challenges in accessing and adhering to treatment, making them a vulnerable population that could greatly benefit from mobile health interventions. In this study, we assessed the feasibility and acceptability of a mobile health application among adolescents and young adults living with HIV. This study was conducted from February to April 2023 in the four health districts within Fako Division. The study utilized a mixed-methods approach to gather comprehensive insights from HIV clients and their healthcare provider. Quantitative data were collected using a structured questionnaire, while qualitative data collection was conducted through focus group discussions (FGDs). Qualitative data was analyzed with Atlas.ti Version9 while the quantitative data analyzed with SPSS Version 25. Among the 119 participants enrolled, 102 (85.7%) demonstrated the ability to read and write while 111 (93.3%) were able to use social media platform. The proportion of participates aged ≤ 19 years who didn’t own a mobile phone was significantly higher (55.4%) among participants, compared to those aged 20–24 years (7.41%) (p = 0.001). Majority (86.6%) expressed the desire to use a mobile health application to facilitate the care and treatment services they receive. Participants expressed desired that software should be able to provide reminders and prevention tips, social corner, drug side effects and appointments. However, they had concerns about the confidentiality of their health information. This study reveals evidence of high proficiency in using mobile applications making it promising for mhealth application to be accepted. However, it also emphasizes the need to prioritize and implement a robust system to ensure privacy and confidentiality during the use of a mobile health application.
Immune checkpoint inhibitor-associated gastrointestinal adverse events in patients with colorectal cancer
Authors: Machado Antonio Pizuorno , Shatila Malek , Aujla Parvir , Huey Ryan , Wang Yinghong , Thomas Anusha
Published: April 2024

Purpose: Immune checkpoint inhibitors (ICI) are currently employed for the management of microsatellite instability-high (MSI-H) tumors with success. While immune checkpoint inhibitor related colitis is a very frequent and a devastating immune related adverse event (irAE) with the use of these agents, the incidence and characteristics of this inflammatory toxicity in patients with MSI-H colorectal cancers has not been examined. We aimed to describe the characteristics and clinical profile of patients diagnosed with luminal gastrointestinal irAE in patients treated with ICI for colorectal cancer in a tertiary cancer care center.
Methods: This is a retrospective analysis that included adult cancer patients diagnosed with colorectal cancer that received ICI between 6/1/2014 and 12/31/2022. We report data on those that developed colitis as an irAE up to 3 months after the last dose of ICI confirmed by laboratory and/or imaging report. We included patients’ demographic characteristics, oncologic profile and outcomes as well as clinical course, endoscopic features as well as treatment and outcomes in terms of luminal gastrointestinal irAEs.
Results: Out of 474 patients with colorectal cancer on ICI in our study period, only 18 developed a gastrointestinal irAE with an incidence of 3.8%. Patients were primarily Caucasian (88.8%) males (61.1%) with a median age of 69.5 years. The majority of these patients received combination therapy with anti-PD-1/L1 and CTLA-4 (50%). 66.6 % received ICI for MSI-H colorectal cancer. 11.1% of our sample were noted to have a second cancer-melanoma. The majority of patients had grade 1-2 colitis (61.2%) and grade 1-2 diarrhea (88.8%). Only 5 patients underwent endoscopic evaluation of whom, 2 had ulcerative inflammation necessitating use of selective immunosuppressive therapy with biologics. 61.1% had to withhold cancer treatment due toxicity. With regards to other gastrointestinal irAEs among this population, 41.4% and 5.8% were noted to have liver and pancreas toxicity respectively, with a median CTCAE grade of severity 2. The majority of our cohort received steroids as therapy.
Conclusion: Luminal gastrointestinal irAEs seem to occur less frequently and at a lower severity among patients with MSI-H colorectal cancer after checkpoint inhibitors exposure compared to the overall incidence of the same among other cancers reported in literature. Larger prospective studies are necessary to determine the role of tumor biology and the gut microbiome in the disease profile and severity of immune related adverse events of the GI organ system.
Nitrogen Isotopes Reveal High NOx Emissions from Arid Agricultural Soils in the Salton Sea Air Basin
Authors: Lieb Heather , Walters Wendell , Maldonado Matthew , Ruiz Edgar , Torres Christian , Olmedo Luis , Faloona Ian
Published: April 2024

Air quality management commonly aims to mitigate emissions of oxides of nitrogen (NOx) from combustion, reducing ozone and particulate matter pollution. Despite such efforts, regulations have recently proven ineffective in rural areas like the Salton Sea Air Basin of Southern California, which routinely violates air quality standards. With $2 billion in annual agricultural sales and low population density, air quality in the region is likely influenced by year-round farming. We conducted NOx source apportionment using nitrogen stable isotopes of ambient NO2, which indicate a substantial contribution of soil-emitted NOx. The soil source strength was estimated based on the mean δ15N-NOx from each emission category in the California Air Resources Board's NOx inventory. Our annual average soil emission estimate for the air basin was 11.4 ± 4 tons/d, representing ~ 30% of the extant NOx inventory, 10× larger than the state’s inventory. Therefore, the impact of soil NOx in agricultural regions must be re-evaluated.
Practice Outcomes for the First Decade of Rural Pharmacy Education (RPHARM) Program Graduates
Authors: OLSON HEIDI , Schriever Allison E. , Rynn Kevin O. , MacDowell Martin
Published: April 2024

Background
The maldistribution of pharmacy services in underserved areas is a national issue. Analysis of data from the 2019 National Pharmacist Workforce Study indicated that 13.9% of pharmacists were working in a rural community. However, the percentage of people living in rural communities in the United States is 20.0%.Currently, there are 20 rural pharmacy programs in the United States, including the Rural Pharmacy Education (RPHARM) Program at the UIC College of Pharmacy, which contain both didactic and experiential rural components. The purpose of this research project is to examine the postgraduate practice outcomes of the RPHARM Program.
Methods
Descriptive analysis was used to examine the practice outcome characteristics of RPHARM Program graduates between 2014 and 2023. The characteristics of the RPHARM graduates included the ruralities of hometowns, practice locations and populations, and distance of practice locations to hometowns. Rural practice outcomes were described utilizing frequently used rural definitions. The practice locations of 54 of the 61 RPHARM graduates were used in the analysis.
Results
Approximately 41% of the practicing RPHARM graduates were from rural hometowns and two-thirds were female. RPHARM graduates mostly work in either a community setting (44.4%) or a hospital setting (37.0%). Approximately 11% worked in a federal government organization and 5.6% worked in a long-term care pharmacy. When examining job movement, 37% of RPHARM graduates have always worked in a rural location as defined by the Federal Office of Rural Health Policy. However, 50% of RPHARM graduates have always worked in urban areas. Approximately 56% of practicing RPHARM graduates are working in a location < 50 miles from their hometown, and 13% are working 50 to 100 miles from their hometown. Approximately 74% of RPHARM graduates are practicing in Illinois.
Conclusions
Approximately 40% of RPHARM graduates practice in rural locations. A significant portion (37%) of RPHARM graduates have always practiced in rural locations, and many (55.5%) are practicing near their hometowns. Results indicate that the RPHARM Program is making meaningful contributions to increasing the rural pharmacy workforce. Due to the lack of information on rural pharmacy practice outcomes, all programs with rural pharmacy content are encouraged to track graduates’ practice locations.
Are species richness and endemism hotspots correlated within a biome? A test case in the fire-impacted subtropical rainforests of Australia
Authors: Torkkola Janne , Hines Harry , Chauvenet Alienor , Oliver Paul
Published: April 2024

Identifying hotspots of particularly rich or localised biodiversity is key strategy for prioritising areas for protection and management. However, different biodiversity measures may lead to the prioritisation of different areas for conservation. Here we use species distribution modelling and spatial biodiversity analyses to map and compare hotspots of Australian subtropical rainforest reptile and amphibian diversity identified using three biodiversity measures - Alpha Diversity, Weighted Endemism, and Corrected Weighted Endemism. Spatial patterns of frog and reptile diversity largely correlate with each other, and with previous studies in plants and other vertebrates, with diversity and endemism both concentrated in montane uplands and correlated with paleoclimatic stability. However Corrected Weighted Endemism highlights additional peripheral hotspots of Short-Range Endemic taxa away from Alpha Diversity hotspots, especially in the poorly known ‘vine-thicket’ habitats of mid-east Queensland. Spatial analyses of the overlap of burn scars from two recent massive fire events show that many of these peripheral hotspots may have been impacted, further highlighting these areas as a priority for targeted survey and conservation assessment.
Bloodstream Infection Due to Corynebacterium striatum: Clinical Characteristics and Outcomes
Authors: He Shu-hua , Chen Yan , Li Shan , Diao Shi-tong , Wang Yi-fan , He Zhuo-xin , Weng Li , Peng Jin-Min , Du Bin
Published: April 2024

Purpose
Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aim to investigate the clinical features and outcomes of C. striatum-BSI.
Methods
We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified into C. striatum-BSI group and contamination group; Clinical characteristics, treatments and outcomes were compared between C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI.
Results
Fifty three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to contaminated group, C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0h vs 42.5h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 hours) when compared to both the MRSA (20 hours) and MRSE groups (19 hours) (p < 0.05). Appropriate therapy within 24 hours of BSI onset was significantly lower in the C. striatum group (28%) compared to the MRSA (64.5%) and MRSE (65.9%) groups (p < 0.005). The 28-day mortality was higher in the C. striatum group (52.0%) compared to the MRSA (25.8%) and MRSE (18.2%) groups.
Conclusions
Given the distinct characteristics of C. striatum-BSI, including a longer time to positivity than other gram-positive bacteria and higher mortality rates, we suggest prescribing early appropriate antibiotics if C. striatum-BSI is suspected.
Shared etiology of Mendelian and complex disease supports drug discovery
Authors: Lalagkas Panagiotis N. , Melamed Rachel D.
Published: April 2024

Background
Drugs targeting disease causal genes are more likely to succeed for that disease. However, complex disease causal genes are not always clear. In contrast, Mendelian disease causal genes are well-known and druggable. Here, we seek an approach to exploit the well characterized biology of Mendelian diseases for complex disease drug discovery, by exploiting evidence of pathogenic processes shared between monogenic and complex disease. One way to find shared disease etiology is clinical association: some Mendelian diseases are known to predispose patients to specific complex diseases (comorbidity). Previous studies link this comorbidity to pleiotropic effects of the Mendelian disease causal genes on the complex disease.
Methods
In previous work studying incidence of 90 Mendelian and 65 complex diseases, we found 2,908 pairs of clinically associated (comorbid) diseases. Using this clinical signal, we can match each complex disease to a set of Mendelian disease causal genes. We hypothesize that the drugs targeting these genes are potential candidate drugs for the complex disease. We evaluate our candidate drugs using information of current drug indications or investigations.
Results
Our analysis shows that the candidate drugs are enriched among currently investigated or indicated drugs for the relevant complex diseases (odds ratio = 1.84, p = 5.98e-22). Additionally, the candidate drugs are more likely to be in advanced stages of the drug development pipeline. We also present an approach to prioritize Mendelian diseases with particular promise for drug repurposing. Finally, we find that the combination of comorbidity and genetic similarity for a Mendelian disease and cancer pair leads to recommendation of candidate drugs that are enriched for those investigated or indicated.
Conclusions
Our findings suggest a novel way to take advantage of the rich knowledge about Mendelian disease biology to improve treatment of complex diseases.
Expanding the cultivated human archaeome by targeted isolation of novel Methanobrevibacter strains from fecal samples
Authors: Moissl-Eichinger Christine , Duller Stefanie , Vrbancic Simone , Szydłowski Łukasz , Mahnert Alexander , Blohs Marcus , Predl Michael , Kumpitsch Christina , Zrim Verena , Högenauer Christoph , Kosciolek Tomasz , Schmitz Ruth , Eberhard Anna , Dragovan Melanie , Schmidberger Laura , Zurabischvili Tamara , Weinberger Viktora , Moser Adrian , Kolb Dagmar , Pernitsch Dominique , Mohammadzadeh Rokhsareh , Kuehnast Torben , Rattei Thomas
Published: April 2024

Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives.
Our study presents a targeted cultivation method enriching methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modelling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyses include co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits.
Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which were absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases.
Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts.
Development of non-antithrombin-mediated heparin resistance models using platelet factor 4 and the effect of antithrombin in these models
Authors: Kitashoji Akira , Kawasaki Natsumi , Komiyama Yutaka , Ieko Masahiro , Kobayashi Fujio
Published: April 2024

Background
Antithrombin (AT) deficiency is considered to be the primary cause of heparin resistance (HR); however, some patients with HR have normal AT activity (non-AT-mediated HR). Supplementation with concentrated human AT is recommended for patients with AT-deficient HR (AT-mediated HR), whereas treatment has not been established for non-AT-mediated HR. Interestingly, the efficacy of concentrated human AT for non-AT-mediated HR has recently been reported. Therefore, this study aimed to investigate the effect of AT in non-AT-mediated HR by developing experimental models using platelet factor 4 (PF4), a potent heparin inhibitor and potential risk factor for non-AT-mediated HR.
Methods
Normal human plasma, mice, and whole blood samples were treated with recombinant PF4 (rPF4), heparin, and AT. Coagulation parameters, including activated partial thromboplastin time (APTT) and clotting time (CT) on rotational thromboelastometry, were assessed. In addition, AT activity of the rPF4-containing plasma was measured, and the interaction of rPF4 or AT with heparin was evaluated.
Results
Treatment with rPF4 shortened APTT and CT prolonged by heparin without reducing AT activity, and AT ameliorated this shortening in a dose-dependent manner. Furthermore, the binding affinity of AT for heparin was weaker than that of rPF4.
Conclusions
We experimentally verified that AT ameliorated non-AT-mediated HR. The potential mechanism was considered to be via increased absolute numbers of AT-heparin complexes. This report provides evidence for therapeutic strategies for non-AT-mediated HR.
Trial registration
Not applicable.
Dramatic loss of microbial viability in bentonite exposed to heat and gamma radiation: Implications for deep geological repository
Authors: Bartak Deepa , Šachlová Šárka , Kašpar Vlastislav , Říha Jakub , Dobrev David , Večerník Petr , Matulová Michaela , Černá Kateřina
Published: April 2024

Bentonite is an integral part of the engineered barrier system (EBS) in deep geological repositories (DGRs) for nuclear waste, but its indigenous microorganisms may jeopardize long-term EBS integrity. To predict microbial activity in DGRs, it is essential to understand microbial reactions to the early hot phase of DGR evolution. Two bentonites (BCV and MX-80) with varied bentonite/water ratios and saturation levels (compacted to 1600 kg.m-3 dry density/powder/suspension), were subjected to heat (90°C or 150°C) and irradiation (0.4 Gy.h-1) in the long-term experiments (up to 18 months). Molecular-genetic, microscopic, and cultivation-based techniques assessed microbial survivability. Exposure to 90°C and 150°C notably diminished microbial viability, irrespective of bentonite form, with negligible impacts from irradiation or sample type compared to temperature. Bentonite powder samples exhibited microbial recovery after 90°C heating for up to 6 months but not 12 months in most cases; exposure to 150°C had an even stronger effect. Further long-term experiments at additional temperatures combined with mathematical prediction of temperature evolution in DGR are recommended to validate the possible evolution and spatial distribution of microbially depleted zones in bentonite buffer around waste canister and refine predictions of microbial effects over time in the DGR.
Preparation of carvacrol β-cyclodextrin inclusions and 1-methylcyclopropene-α-CD coated paper by water-free method for postharvest preservation of peach
Authors: Cao Zhaoxin , Su Jingyi , Luo Yali , Wang Xinyu , Liu Zhiming , Chen Yanqi , Zou Yijing , Shen Wen , Ge Xuemei
Published: April 2024

Carvacrol essential oil has broad-spectrum antibacterial properties, but the essential oil is volatile and unstable for long term storage and using. In order to improve the relevant properties of carvacrol, in the present study, carvacrol was encapsulated with β-cyclodextrin (β-CD) using the saturated aqueous solution method and response surface analysis was carried out, which gave a high encapsulation rate (63.58%). The success encapsulation of carvacrol was confirmed by scanning electron microscopy, Fourier infrared spectroscopy, X-ray diffraction and thermogravimetric analysis. The release performance of the encapsulants was also tested at different temperature and humidity levels. In addition, Polyethylene glycol (PEG) composite carvacrol-inclusive fresh-keeping paper prepared by these anhydrous conditions showed high antibacterial activity against Streptomyces fructus Monilinia fructicola, the main pathogen of peaches. Also, PEG was used to form the film in the anhydrous condition with the inclusion compound and ethylene inhibitor 1-methylcyclopropene (1-MCP) to obtain the film coated paper, and its effect on postharvest preservation quality of peach was studied. The results showed that PEG + Carvacrol-β-CD + 1-MCP-α-CD inclusion complexes (ICs) effectively prolonged the storage time and improved the fruit quality and enzyme activity of peach. This study provides a solution for the preparation of controlled-release coated paper with essential oils and 1-MCP bioactives to extend the shelf life of fruits and vegetables.
Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1
Authors: Adachi Yuki , Noguchi Rei , Osaki Julia , Ono Takuya , Iwata Shuhei , Akiyama Taro , Tsuchiya Ryuto , Toda Yu , Sekita Tetsuya , Iwata Shintaro , Kobayashi Eisuke , Kojima Naoki , Yoshida Akihiko , Yokoo Hideki , Kawai Akira , Kondo Tadashi
Published: April 2024

Myxofibrosarcoma (MFS), an aggressive soft tissue sarcoma, presents a significant challenge because of its high recurrence rate, distal metastasis, and complex genetic background. Although surgical resection is the standard treatment for MFS, the outcomes are unsatisfactory, and effective non-surgical treatment strategies, including drug therapy, are urgently warranted. MFS is a rare tumor that requires comprehensive preclinical research to develop promising drug therapies; however, only two MFS cell lines are publicly available worldwide. The present study reports two novel patient-derived MFS cell lines, NCC-MFS7-C1 and NCC-MFS8-C1. These cell lines have been extensively characterized for their genetic profile, proliferation, spheroid-forming capacity, and invasive behavior, confirming that they retain MFS hallmarks. Furthermore, we conducted comprehensive drug screening against these cell lines and six others previously established in our laboratory to identify potential therapeutic candidates for MFS. Among the screened agents, actinomycin D, bortezomib, and romidepsin demonstrated considerable antiproliferative effects that were superior to those of doxorubicin, a standard drug, highlighting their potential as novel drugs. In conclusion, NCC-MFS7-C1 and NCC-MFS8-C1 are valuable research resources that contribute to the understanding of the pathogenesis and development of novel therapies for MFS.
Postural misalignments in school students: comparisons between gender, school cycles and body composition
Authors: Gouveia João Pedro , Coelho Eduarda , Forte Pedro
Published: April 2024

The prevalence of postural misalignments in children and young people is markedly increasing and schools can play a leading role in its early detection. This study aimed to carry out a postural assessment of the spine and shoulder and pelvic girdles in 162 school students (82 males and 80 females), aged between 10 and 15 years, comparing, afterwards, these postural misalignments between gender, schooling cycles and body composition. A symmetrograph was used to carry out the postural assessment by visual scan analysis and the Adams Test. All subjects revealed a high percentage of postural misalignments. The highest prevalence was observed in the posterior view of the frontal plane in the right shoulder elevation, dorsal and cervical scoliosis, whereas, in the right view of the sagittal plane forward head posture, protracted shoulders and dorsal hyperkyphosis were the most observed. The main findings in the comparison between gender were that males revealed significantly higher levels of shoulder protrusion (X2 = 13.508; p = 0.001), dorsal hyperkyphosis (X2 = 10.080; p = 0.006) and positive Adams test (X2 = 9.481; p = 0.009). Between schooling cycles, 3rd cycle students revealed significantly higher levels of forward head posture (X2 = 10.603; p = 0.001), dorsal hyperkyphosis (X2 = 8.314; p = 0.016) and lumbar scoliosis (X2 = 7.752; p = 0.005), while those in the 2nd showed greater pelvic anteversion (X2 = 20.109; p < 0.001). Students outside the body mass index (BMI) healthy zone demonstrated significantly higher levels of forward head posture (X2 = 6.821; p = 0.033), dorsal hyperkyphosis (X2 = 14,727; p = 0.005) and pelvic anteversion (X2 = 10.156; p = 0.038), the latter being also significantly evidenced by those outside the body fat percentage (BF%) healthy zone (X2 = 12.371; p = 0.015). A wide variety of postural misalignments was found in both genders, with a higher prevalence in boys. There was a tendency for misalignment’s prevalence increase with the schooling cycles progression, as well as the highest levels of obesity seem to be related with their highest prevalence. These results strongly emphasize the need and the importance of postural assessment in physical education (PE) classes to determine postural misalignments among school students.
Characterization of Fatigue Behavior of 3D Printed Pneumatic Fluidic Elastomer Actuators
Authors: Torzini Lorenzo , Puggelli Luca , Volpe Yary , Governi Lapo , buonamici francesco
Published: April 2024

Soft robots have gained significant interest over the past two decades due to their high flexibility and adaptability to various working conditions. Recent advances in engineering and innovative materials have enabled the design and production of sophisticated soft robotic systems with enhanced capabilities. Additive manufacturing has accelerated the development of soft actuators, unlocking complex kinematics, improving their effectiveness and allowing the production of task-specific actuators. 3D printed soft actuators can gain advantage of the fabricability of complex geometries to guarantee improved mobility and grasping abilities. However, challenges remain in investigating the durability of such devices. Limits of most recent advanced manufacturing methods and materials, with this respect, are still to be fully explored.In this work, bellow-type pneumatic soft actuators fabricated through Fused Filament Fabrication in thermoplastic polyurethane (TPU) are tested to evaluate their fatigue behaviour. Silicone rubber casted actuators are included to provide a point of reference. The actuators integrated resistive flex sensors to monitor bending motion. Fatigue tests were performed with cycles of inflation and deflation until failure. Results showed that 3D printed TPU actuators are capable of whitstanding a significant amount of cycles before failure, ultimately being comparable with alternative fabrication technologies. Overall, this study proves the potential of the Fused Filament Fabrication process for the fabrication of durable, long-lasting pneumatic soft actuators.
Effective Method of Pedicle Screw Fixation in Patients with Neurologically Intact Thoracolumbar Burst Fractures: A Systematic Review of Studies Published Over the Last 20 Years
Authors: Grin Andrey , Karanadze Vasiliy , Kordonskiy Anton , Talypov Aleksandr , Lvov Ivan
Published: April 2024

Objective: To conduct a systematic review of studies focusing on various PSF methods for neurologically intact burst fractures of the thoracic and lumbar spine (TLFS) and identify the most effective and safe approach among them.
Methods. Systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study was registered in the PROSPERO (№ CRD42024531093). The inclusion criteria for articles in the systematic review were as follows: 1) publication date between January 1, 2004, and December 31, 2023; 2) availability of the full-text version of the article in English; 3) fracture type A3 or A4 according to the AOSpine classification, or types A, B, or C burst fractures according to the F. Denis classification, or direct indication by the author of the presence of a "burst" fracture without its classification; 4) absence of neurological deficit; 5) patient age over 18 years; 6) description of treatment outcomes or complications; 7) follow-up period of 12 months for patient samples.
Results. In total, the 70 articles presented treatment results for 122 groups of patients were included. Statistical analysis demonstrated the advantages of short-segment fixation in terms of operation duration and intraoperative blood loss (p = 0.001 and < 0.001, respectively). It was also found that the frequency of deep infection was significantly higher with extensive fusion compared to other PSF methods (p = 0.043). Percutaneous pedicle screw fixation (PSF) was performed in patients with lower body compression rate and kyphotic deformity values (p = 0.043), had less potential for their correction (p = 0.004), but significantly reduced blood loss (p = 0.011), operation duration (p < 0.0001), and hospitalization period (p < 0.0001). Statistical analysis did not reveal significant advantages of using additional intermediate screws in patients undergoing short-segment PSF.
Conclusions. The optimal surgical treatment method for neurologically intact thoracolumbar burst fractures is short-segment, 4-screw pedicle screw fixation. The use of posterior lateral fusion in this context may increase the deep infection rate without reducing the frequency of implant-related complications or affecting long-term treatment outcomes. Percutaneous approach is the preferred technique; however, in patients with severe kyphotic deformities, its lower reduction capabilities should be considered during surgical planning. The application of intermediate screws in patients with neurologically intact thoracolumbar burst fractures did not demonstrate any significant advantages. Removal of the fixation system did not lead to a significant reduction in implant-related complications or improvement in quality of life.
Deficient DNA mismatch repair status reveals good prognosis for non-metastatic signet ring cell (SRC) subpopulation
Authors: Chen Yongjiu , Li Yingjie , Sun Tingting , Ji Dengbo , Jia Jinying , Hu Fangjie , Pei Junpeng , Wang Lin , Wu Aiwen
Published: April 2024

Purpose
As a rare subpopulation of colorectal cancer (CRC), signet ring cell carcinoma (SRCC) has poor prognosis. The prognostic role of DNA mismatch repair (MMR) has been seldom studied. Thus, to analyze the effect of MMR status on survival outcomes in colorectal SRCC patients, we conducted this retrospective study.
Method
DNA mismatch repair status was performed on 114 patients via IHC. Prognostic clinicopathologic parameters of deficient or proficient DNA mismatch repair status were compared by the chi-squared test. Survival outcomes (OS, DFS) were measured via the Kaplan-Meier LIFETEST and the log-rank test. The multivariate survival analysis was evaluated by the Cox proportional-hazards regression model, and the hazard ratio (HR) with 95% CI was provided.
Results
Among 7343 colorectal cancer patients from 2009 to 2020, there were 176 patients with SRCC, nearly one quarter (23.7%, 27/114) harbored dMMR. Besides, dMMR SRCC patients are more often located in the rectum (51.1%). No difference was found for metastatic disease while dMMR had relatively good prognosis for non-metastatic with a median follow-up of 71.9 months (13.9 to 155). The overall 3- and 5-year OS were 42.1% and 32.1%, respectively, while the 3- and 5-year DFS were 43.0% and 32.9%, respectively. Moreover, the multivariate survival analysis via Cox proportional-hazards model revealed MMR status was an independent prognostic for colorectal SRCC.
Conclusion
Nearly one quarter patients harbored dMMR and relatively better survival outcomes than pMMR in this colorectal SRCC cohort. Early identification of this subgroup may be of importance for the survival of SRCC patients.