bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching Medical Students Rapid Ultrasound for shock and hypotension (RUSH): learning outcomes and clinical performance in a proof-of-concept study
Authors: Müller-Wirtz Lukas Martin , Patterson William M. , Ott Sascha , Brauchle Annika , Meiser Andreas , Volk Thomas , Berwanger Ulrich , Conrad David
Published: April 2024

Background

Point-of-care ultrasound (POCUS) is a critical diagnostic tool in various medical settings, yet its instruction in medical education is inconsistent. The Rapid Ultrasound for Shock and Hypotension (RUSH) protocol is a comprehensive diagnostic tool, but its complexity poses challenges for teaching and learning. This study evaluates the effectiveness of a single-day training in RUSH for medical students by assessing their performance in clinical scenarios.

Methods

In this prospective single-center observational proof-of-concept study, 16 medical students from Saarland University Medical Center underwent a single-day training in RUSH, followed by evaluations in clinical settings and on a high-fidelity simulator. Performance was assessed using a standardized scoring tool and time to complete the RUSH exam. Knowledge gain was measured with pre- and post-training written exams, and diagnostic performance was evaluated with an objective structured clinical examination (OSCE).

Results

Students demonstrated high performance in RUSH exam views across patients (median performance: 85–87%) and improved scanning times, although not statistically significant. They performed better on simulators than on live patients. Written exam scores significantly improved post-training, suggesting a gain in theoretical knowledge. However, more than a third of students could not complete the RUSH exam within five minutes on live patients.

Conclusions

Single-day RUSH training improved medical students’ theoretical knowledge and simulator performance but translating these skills to clinical settings proved challenging. The findings suggest that while short-term training can be beneficial, it may not suffice for clinical proficiency. This study underscores the need for structured and possibly longitudinal training programs to ensure skill retention and clinical applicability.
Implementing digital sexual and reproductive health care services in youth clinics: a qualitative study on perceived barriers and facilitators among midwives in Stockholm, Sweden
Authors: Zettergren Linn , Larsson Elin C. , Hellsten Lovisa , Kosidou Kyriaki , Nielsen Anna Maria
Published: April 2024

Background

Digital health care services have the potential to improve access to sexual and reproductive health care for youth but require substantial implementation efforts to translate into individual and public health gains. Health care providers are influential both regarding implementation and utilization of the services, and hence, their perceptions of digital health care services and the implementation process are essential to identify and address. The aim of this study was to explore midwives’ perception of digital sexual and reproductive health care services for youth, and to identify perceived barriers and facilitators of the implementation of digital health care provision in youth clinics.

Methods

We performed semi-structured interviews with midwives (n = 16) working at youth clinics providing both on-site and digital sexual and reproductive health care services to youth in Stockholm, Sweden. Interview data were analyzed using a content analysis approach guided by the Consolidated Framework for Implementation Research (CFIR).

Results

Midwives acknowledged that the implementation of digital health care improved the overall access and timeliness of the services at youth clinics. The ability to accommodate the needs of youth regarding their preferred meeting environment (digital or on-site) and easy access to follow-up consultations were identified as benefits of digital health care. Challenges to provide digital health care included communication barriers, privacy and confidentiality concerns, time constraints, inability to offer digital appointments for social counselling, and midwives’ preference for in person consultations. Experiencing organizational support during the implementation was appreciated but varied between the respondents.

Conclusion

Digital sexual and reproductive health care services could increase access and are valuable complements to on-site services in youth clinics. Sufficient training for midwives and organizational support are crucial to ensure high quality health care. Privacy and safety concerns for the youth might aggravate implementation of digital health care. Future research could focus on equitable access and youth’ perceptions of digital health care services for sexual and reproductive health.
Biochemical and molecular characterization of Campylobacter fetus isolates from bulls subjected to bovine genital campylobacteriosis diagnosis in Spain
Authors: Pena-Fernández Nerea , Kortabarria Nekane , Hurtado Ana , Ocejo Medelin , Fort Marcelo , Pérez-Cobo Iratxe , Collantes-Fernández Esther , Aduriz Gorka
Published: April 2024

Background

Bovine genital campylobacteriosis (BGC) is caused by Campylobacter fetus subsp. venerealis (Cfv) including its biovar intermedius (Cfvi). This sexually transmitted disease induces early reproductive failure causing considerable economic losses in the cattle industry. Using a collection of well-characterized isolates (n = 13), C. fetus field isolates (n = 64) and saprophytic isolates resembling Campylobacter (n = 75) obtained from smegma samples of breeding bulls, this study evaluated the concordance of the most used phenotypic (H2S production in cysteine medium and 1% glycine tolerance) and molecular (PCR) methods for the diagnosis of BGC and assessed possible cross-reactions in the molecular diagnostic methods.

Results

Characterization at the subspecies level (fetus vs. venerealis) of C. fetus isolated from bull preputial samples using phenotypic and molecular (PCR targeting nahE and ISCfe1) methods showed moderate concordance (κ = 0.462; CI: 0.256–0.669). No cross-reactions were observed with other saprophytic microaerophilic species or with other Campylobacter species that can be present in preputial samples. Whole genome sequencing (WGS) of discrepant isolates showed 100% agreement with PCR identification. For the differentiation of Cfv biovars, comparison of the H2S test (at 72 h and 5 days of incubation) and a PCR targeting the L-cysteine transporter genes showed higher concordance when H2S production was assessed after 5 days (72 h; κ = 0.553, 0.329–0.778 CI vs. 5 days; κ = 0.881, 0.631–1 CI), evidencing the efficacy of a longer incubation time.

Conclusions

This study confirmed the limitations of biochemical tests to correctly identify C. fetus subspecies and biovars. However, in the case of biovars, when extended incubation times for the H2S test (5 days) were used, phenotypic identification results were significantly improved, although PCR-based methods produced more accurate results. Perfect agreement of WGS with the PCR results and absence of cross-reactions with non-C. fetus saprophytic bacteria from the smegma demonstrated the usefulness of these methods. Nevertheless, the identification of new C. fetus subspecies-specific genes would help to improve BGC diagnosis.
Research advances in the identification of regulatory mechanisms of surfactin production by Bacillus: a review
Authors: Qiao Junqing , Borriss Rainer , Sun Kai , Zhang Rongsheng , Chen Xijun , Liu Youzhou , Liu Yongfeng
Published: April 2024

Surfactin is a cyclic hexalipopeptide compound, nonribosomal synthesized by representatives of the Bacillus subtilis species complex which includes B. subtilis group and its closely related species, such as B. subtilis subsp subtilis, B. subtilis subsp spizizenii, B. subtilis subsp inaquosorum, B. atrophaeus, B. amyloliquefaciens, B. velezensis (Steinke mSystems 6: e00057, 2021) It functions as a biosurfactant and signaling molecule and has antibacterial, antiviral, antitumor, and plant disease resistance properties. The Bacillus lipopeptides play an important role in agriculture, oil recovery, cosmetics, food processing and pharmaceuticals, but the natural yield of surfactin synthesized by Bacillus is low. This paper reviews the regulatory pathways and mechanisms that affect surfactin synthesis and release, highlighting the regulatory genes involved in the transcription of the srfAA-AD operon. The several ways to enhance surfactin production, such as governing expression of the genes involved in synthesis and regulation of surfactin synthesis and transport, removal of competitive pathways, optimization of media, and fermentation conditions were commented. This review will provide a theoretical platform for the systematic genetic modification of high-yielding strains of surfactin.

Graphical Abstract
Risk factors of 30-day and long-term mortality and outcomes in open repair of thoracoabdominal aortic aneurysm
Authors: Wang Sudena , Wang Chunrong , Gao Yuchen , Tian Yu , Liu Jia , Wang Yuefu
Published: April 2024

Background

Open repair of thoracoabdominal aortic aneurysm (TAAA) was characterized by significant risk of postoperative mortality and morbidity. The aim of this study was to determine the perioperative predictors of early and long-term mortality in patients undergoing open repair of TAAA. Besides, the postoperative outcomes in patients with open repair of TAAA were described.

Methods

This is a single-center retrospective study, and 146 patients with open repair of TAAA from January 4, 2011, to November 22, 2018 was involved. Categorical variables were analyzed by the Chi-square test or Fisher’s exact test, and continuous variables were analyzed by the independent sample t-test and the WilCoxon rank-sum test. Multivariate Logistic regression and Cox regression were applied to identify the predictors of 30-day and long-term mortality, respectively. The Kaplan Meier curves were used to illustrate survival with the Log-rank test.

Results

The 30-day mortality was 9.59% (n = 14). Older than 50 years, the intraoperative volume of red blood cell (RBC) and epinephrine use were independently associated with postoperative 30-day mortality in open repair of TAAA. Long-term mortality was 17.12% (n = 25) (median of 3.5 years (IQR = 2–5 years) of follow-up). Prior open thoracoabdominal aortic aneurysm (TAAA) repair, aortic cross-clamping (ACC) time, intraoperative volume of RBC and use of epinephrine were independently correlated with long-term mortality.

Conclusions

Identifying perioperative risk factors of early and long-term mortaliy is crucial for surgeons. Intraoperative volume of RBC and use of epinephrine were predictors of both early and long-term mortality. In addition, patients of advanced age, prior open repair of TAAA and prolonged ACC time should be paid more attention.
‘Nowhere and no one is safe’: spatial analysis of damage to critical civilian infrastructure in the Gaza Strip during the first phase of the Israeli military campaign, 7 October to 22 November 2023
Authors: Asi Yara , Mills David , Greenough P. Gregg , Kunichoff Dennis , Khan Saira , Hoek Jamon Van Den , Scher Corey , Halabi Saleem , Abdulrahim Sawsan , Bahour Nadine , Ahmed A. Kayum , Wispelwey Bram , Hammoudeh Weeam
Published: April 2024

Background

Since the Hamas attacks in Israel on 7 October 2023, the Israeli military has launched an assault in the Gaza Strip, which included over 12,000 targets struck and over 25,000 tons of incendiary munitions used by 2 November 2023. The objectives of this study include: (1) the descriptive and inferential spatial analysis of damage to critical civilian infrastructure (health, education, and water facilities) across the Gaza Strip during the first phase of the military campaign, defined as 7 October to 22 November 2023 and (2) the analysis of damage clustering around critical civilian infrastructure to explore broader questions about Israel’s adherence to International Humanitarian Law (IHL).

Methods

We applied multi-temporal coherent change detection on Copernicus Sentinel 1-A Synthetic Aperture Radar (SAR) imagery to detect signals indicative of damage to the built environment through 22 November 2023. Specific locations of health, education, and water facilities were delineated using open-source building footprint and cross-checked with geocoded data from OCHA, OpenStreetMap, and Humanitarian OpenStreetMap Team. We then assessed the retrieval of damage at and with close proximity to sites of health, education, and water infrastructure in addition to designated evacuation corridors and civilian protection zones. The Global Moran’s I autocorrelation inference statistic was used to determine whether health, education, and water facility infrastructure damage was spatially random or clustered.

Results

During the period under investigation, in the entire Gaza Strip, 60.8% (n = 59) of health, 68.2% (n = 324) of education, and 42.1% (n = 64) of water facilities sustained infrastructure damage. Furthermore, 35.1% (n = 34) of health, 40.2% (n = 191) of education, and 36.8% (n = 56) of water facilities were functionally destroyed. Applying the Global Moran’s I spatial inference statistic to facilities demonstrated a high degree of damage clustering for all three types of critical civilian infrastructure, with Z-scores indicating < 1% likelihood of cluster damage occurring by random chance.

Conclusion

Spatial statistical analysis suggests widespread damage to critical civilian infrastructure that should have been provided protection under IHL. These findings raise serious allegations about the violation of IHL, especially in light of Israeli officials’ statements explicitly inciting violence and displacement and multiple widely reported acts of collective punishment.
Potential mental health-related harms associated with the universal screening of anxiety and depressive symptoms in Australian secondary schools
Authors: Braund Taylor A. , Baker Simon T. E. , Subotic-Kerry Mirjana , Tillman Gabriel , Evans Nathan J. , Mackinnon Andrew , Christensen Helen , O’Dea Bridianne
Published: April 2024

Background

Anxiety and depressive disorders typically emerge in adolescence and can be chronic and disabling if not identified and treated early. School-based universal mental health screening may identify young people in need of mental health support and facilitate access to treatment. However, few studies have assessed the potential harms of this approach. This paper examines some of the potential mental health-related harms associated with the universal screening of anxiety and depression administered in Australian secondary schools.

Methods

A total of 1802 adolescent students from 22 secondary schools in New South Wales, Australia, were cluster randomised (at the school level) to receive either an intensive screening procedure (intervention) or a light touch screening procedure (control). Participants in the intensive screening condition received supervised self-report web-based screening questionnaires for anxiety, depression and suicidality with the follow-up care matched to their symptom severity. Participants in the light touch condition received unsupervised web-based screening for anxiety and depression only, followed by generalised advice on help-seeking. No other care was provided in this condition. Study outcomes included the increased risk of anxiety, depression, psychological distress, decreased risk of help-seeking, increased risk of mental health stigma, determined from measures assessed at baseline, 6 weeks post-baseline, and 12 weeks post-baseline. Differences between groups were analysed using mixed effect models.

Results

Participants in the intensive screening group were not adversely affected when compared to the light touch screening condition across a range of potential harms. Rather, participants in the intensive screening group were found to have a decreased risk of inhibited help-seeking behaviour compared to the light touch screening condition.

Conclusions

The intensive screening procedure did not appear to adversely impact adolescents’ mental health relative to the light touch procedure. Future studies should examine other school-based approaches that may be more effective and efficient than universal screening for reducing mental health burden among students.

Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12618001539224) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375821.
Investigating the impact of regulatory B cells and regulatory B cell-related genes on bladder cancer progression and immunotherapeutic sensitivity
Authors: Zhou Jiawei , Zhou Ranran , Zhu Yuanchao , Deng Shikai , Muhuitijiang Bahaerguli , Li Chengyao , Shi Xiaojun , Zhang Ling , Tan Wanlong
Published: April 2024

Background

Regulatory B cells (Bregs), a specialized subset of B cells that modulate immune responses and maintain immune tolerance in malignant tumors, have not been extensively investigated in the context of bladder cancer (BLCA). This study aims to elucidate the roles of Bregs and Breg-related genes in BLCA.

Methods

We assessed Breg infiltration levels in 34 pairs of BLCA and corresponding paracancerous tissues using immunohistochemical staining. We conducted transwell and wound healing assays to evaluate the impact of Bregs on the malignant phenotype of SW780 and T24 cells. Breg-related genes were identified through gene sets and transcriptional analysis. The TCGA-BLCA cohort served as the training set, while the IMvigor210 and 5 GEO cohorts were used as external validation sets. We employed LASSO regression and random forest for feature selection and developed a risk signature using Cox regression. Primary validation of the risk signature was performed through immunohistochemical staining and RT-qPCR experiments using the 34 local BLCA samples. Additionally, we employed transfection assays and flow cytometry to investigate Breg expansion ability and immunosuppressive functions.

Results

Breg levels in BLCA tissues were significantly elevated compared to paracancerous tissues (P < 0.05) and positively correlated with tumor malignancy (P < 0.05). Co-incubation of SW780 and T24 cells with Bregs resulted in enhanced invasion and migration abilities (all P < 0.05). We identified 27 Breg-related genes, including CD96, OAS1, and CSH1, which were integrated into the risk signature. This signature demonstrated robust prognostic classification across the 6 cohorts (pooled HR = 2.25, 95% CI = 1.52–3.33). Moreover, the signature exhibited positive associations with advanced tumor stage (P < 0.001) and Breg infiltration ratios (P < 0.05) in the local samples. Furthermore, the signature successfully predicted immunotherapeutic sensitivity in three cohorts (all P < 0.05). Knockdown of CSH1 in B cells increased Breg phenotype and enhanced suppressive ability against CD8 + T cells (all P < 0.05).

Conclusions

Bregs play a pro-tumor role in the development of BLCA. The Breg-related gene signature established in this study holds great potential as a valuable tool for evaluating prognosis and predicting immunotherapeutic response in BLCA patients.
Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells
Authors: Lee Juwon , Jang Suin , Im Jihye , Han Youngjin , Kim Soochi , Jo HyunA , Wang Wenyu , Cho Untack , Kim Se Ik , Seol Aeran , Kim Boyun , Song Yong Sang
Published: April 2024

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.
Bento: a toolkit for subcellular analysis of spatial transcriptomics data
Authors: Mah Clarence K. , Ahmed Noorsher , Lopez Nicole A. , Lam Dylan C. , Pong Avery , Monell Alexander , Kern Colin , Han Yuanyuan , Prasad Gino , Cesnik Anthony J. , Lundberg Emma , Zhu Quan , Carter Hannah , Yeo Gene W.
Published: April 2024

The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell–cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit that takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three analyses: defining subcellular domains, annotating localization patterns, and quantifying gene–gene colocalization. We demonstrate MERFISH, seqFISH + , Molecular Cartography, and Xenium datasets. Bento is part of the open-source Scverse ecosystem, enabling integration with other single-cell analysis tools.
Species-aware DNA language models capture regulatory elements and their evolution
Authors: Karollus Alexander , Hingerl Johannes , Gankin Dennis , Grosshauser Martin , Klemon Kristian , Gagneur Julien
Published: April 2024

Background

The rise of large-scale multi-species genome sequencing projects promises to shed new light on how genomes encode gene regulatory instructions. To this end, new algorithms are needed that can leverage conservation to capture regulatory elements while accounting for their evolution.

Results

Here, we introduce species-aware DNA language models, which we trained on more than 800 species spanning over 500 million years of evolution. Investigating their ability to predict masked nucleotides from context, we show that DNA language models distinguish transcription factor and RNA-binding protein motifs from background non-coding sequence. Owing to their flexibility, DNA language models capture conserved regulatory elements over much further evolutionary distances than sequence alignment would allow. Remarkably, DNA language models reconstruct motif instances bound in vivo better than unbound ones and account for the evolution of motif sequences and their positional constraints, showing that these models capture functional high-order sequence and evolutionary context. We further show that species-aware training yields improved sequence representations for endogenous and MPRA-based gene expression prediction, as well as motif discovery.

Conclusions

Collectively, these results demonstrate that species-aware DNA language models are a powerful, flexible, and scalable tool to integrate information from large compendia of highly diverged genomes.
A key gene, violaxanthin de-epoxidase-like 1, enhances fucoxanthin accumulation in Phaeodactylum tricornutum
Authors: Li Chenjie , Pan Yufang , Yin Wenxiu , Liu Jin , Hu Hanhua
Published: April 2024

Background

Fucoxanthin has been widely investigated owing to its beneficial biological properties, and the model diatom Phaeodactylum tricornutum, possessing fucoxanthin (Fux) chlorophyll proteins as light-harvesting systems, is considered to have the potential to become a commercial cell factory for the pigment production.

Results

Here, we compared the pigment contents in 10 different P. tricornutum strains from the globe, and found that strain CCMP631 (Pt6) exhibited the highest Fux content but with a low biomass. Comparison of mRNA levels revealed that higher Fux content in Pt6 was related with the higher expression of gene violaxanthin de-epoxidase-like (VDL) protein 1 (VDL1), which encodes the enzyme catalyzing the tautomerization of violaxanthin to neoxanthin in Fux biosynthesis pathway. Single nucleotide variants of VDL1 gene and allele-specific expression in strains Pt1 (the whole genome sequenced strain CCMP632) and Pt6 were analyzed, and overexpressing of each of the 4 VDL1 alleles, two from Pt1 and two from Pt6, in strain Pt1 leads to an increase in downstream product diadinoxanthin and channels the pigments towards Fux biosynthesis. All the 8 VDL1 overexpression (OE) lines showed significant increases by 8.2 to 41.7% in Fux content without compromising growth, and VDL1 Allele 2 OE lines even exhibited the higher cell density on day 8, with an increase by 24.2–28.7% in two Pt1VDL1-allele 2 OE lines and 7.1–11.1% in two Pt6VDL1-allele 2 OE lines, respectively.

Conclusions

The results reveal VDL1, localized in the plastid stroma, plays a key role in Fux over-accumulation in P. tricornutum. Overexpressing VDL1, especially allele 2, improved both the Fux content and growth rate, which provides a new strategy for the manipulation of Fux production in the future.
Concordance between two monoclonal antibody-based antigen detection enzyme-linked immunosorbent assays for measuring cysticercal antigen levels in sera from pigs experimentally infected with Taenia solium and Taenia hydatigena
Authors: Arroyo Gianfranco , Toribio Luz , Garrido Sara , Chile Nancy , Lopez-Urbina Teresa , Gomez-Puerta Luis A. , Muro Miguel , Gilman Robert H. , Castillo Yesenia , Dorny Pierre , O’Neal Seth E. , Gonzalez Armando E. , Garcia Hector H. ,   for The Cysticercosis Working Group in Peru (CWGP)
Published: April 2024

Background

Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA.

Methods

We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland–Altman (BA) analysis and Lin’s concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA.

Results

The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin’s CCC: 0.69, 0.92, and 0.96, respectively, all P < 0.001). In pigs infected with T. hydatigena, almost all paired log-OD differences were within the LoA in the BA analysis, whereas the concordance of log-ODs between assays was low at baseline (Lin’s CCC: 0.24) but increased on days 28 and 90 PI (Lins’ CCC: 0.88 and 0.98, P < 0.001).

Conclusions/significance

The TsW8/TsW5 Ag-ELISA recognizes antigens in pigs with T. solium cysticercosis and is highly concordant with the B158/B60 Ag-ELISA. However, its diagnostic use is hampered by cross-reactions with T. hydatigena, as in other mAb-based Ag-ELISAs.

Graphical Abstract
Tick-borne bacterial agents in Hyalomma asiaticum ticks from Xinjiang Uygur Autonomous Region, Northwest China
Authors: Zhang Bing , Zhang Niuniu , Zheng Tao , Lu Miao , Baoli Bierk , Jie Runda , Wang Xiao , Li Kun
Published: April 2024

Background

Hyalomma ticks are widely distributed in semi-arid zones in Northwest China. They have been reported to harbor a large number of zoonotic pathogens.

Methods

In this study, a total of 334 Hyalomma asiaticum ticks infesting domestic animals were collected from four locations in Xinjiang, Northwest China, and the bacterial agents in them were investigated.

Results

A putative novel Borrelia species was identified in ticks from all four locations, with an overall positive rate of 6.59%. Rickettsia sibirica subsp. mongolitimonae, a human pathogen frequently reported in Europe, was detected for the second time in China. Two Ehrlichia species (Ehrlichia minasensis and Ehrlichia sp.) were identified. Furthermore, two Anaplasma species were characterized in this study: Candidatus Anaplasma camelii and Anaplasma sp. closely related to Candidatus Anaplasma boleense. It is the first report of Candidatus Anaplasma camelii in China.

Conclusions

Six bacterial agents were reported in this study, many of which are possible or validated pathogens for humans and animals. The presence of these bacterial agents may suggest a potential risk for One Health in this area.

Graphical Abstract
Association between environmental gradient of anthropization and phenotypic plasticity in two species of triatomines
Authors: Fiad Federico G. , Cardozo Miriam , Nattero Julieta , Gigena Gisel V. , Gorla David E. , Rodríguez Claudia S.
Published: April 2024

Background

Triatoma garciabesi and T. guasayana are considered secondary vectors of Trypanosoma cruzi and frequently invade rural houses in central Argentina. Wing and head structures determine the ability of triatomines to disperse. Environmental changes exert selective pressures on populations of both species, promoting changes in these structures that could have consequences for flight dispersal. The aim of this study was to investigate the relationship between a gradient of anthropization and phenotypic plasticity in flight-related traits.

Methods

The research was carried out in Cruz del Eje and Ischilín departments (Córdoba, Argentina) and included 423 individuals of the two species of triatomines. To measure the degree of anthropization, a thematic map was constructed using supervised classification, from which seven landscapes were selected, and nine landscape metrics were extracted and used in a hierarchical analysis. To determine the flight capacity and the invasion of dwellings at different levels of anthropization for both species, entomological indices were calculated. Digital images of the body, head and wings were used to measure linear and geometric morphometric variables related to flight dispersion. One-way ANOVA and canonical variate analysis (CVA) were used to analyze differences in size and shape between levels of anthropization. Procrustes variance of shape was calculated to analyze differences in phenotypic variation in heads and wings.

Results

Hierarchical analysis was used to classify the landscapes into three levels of anthropization: high, intermediate and low. The dispersal index for both species yielded similar results across the anthropization gradient. However, in less anthropized landscapes, the density index was higher for T. garciabesi. Additionally, in highly anthropized landscapes, females and males of both species exhibited reduced numbers. Regarding phenotypic changes, the size of body, head and wings of T. garciabesi captured in the most anthropized landscapes was greater than for those captured in less anthropized landscapes. No differences in body size were observed in T. guasayana collected in the different landscapes. However, males from highly anthropized landscapes had smaller heads and wings than those captured in less anthropized landscapes. Both wing and head shapes varied between less and more anthropogenic environments in both species.

Conclusions

Results of the study indicate that the flight-dispersal characteristics of T. garciabesi and T. guasayana changed in response to varying degrees of anthropization.

Graphical Abstract
Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response
Authors: Qin Qingqing , Zhou Ying , Guo Jintao , Chen Qinwei , Tang Weiwei , Li Yuchen , You Jun , Li Qiyuan
Published: April 2024

Background

Aberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes.

Methods

We performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts.

Results

We identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment.

Conclusions

Our findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.
Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression
Authors: Chen Zegeng , Huang He , Hong Huangming , Huang Huageng , Weng Huawei , Yu Le , Xiao Jian , Wang Zhao , Fang Xiaojie , Yao Yuyi , Yue Jia-Xing , Lin Tongyu
Published: April 2024

Background

Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored.

Methods

Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels.

Results

Our study not only confirmed previously reported common NKTCL mutational targets likeSTAT3,TP53, andDDX3Xbut also unveiled several novel high-frequency mutational targets such asPRDM9,DST, andRBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0–C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole.

Conclusions

The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.
Association between stress hyperglycemia ratio and diabetes mellitus mortality in American adults: a retrospective cohort study and predictive model establishment based on machine learning algorithms (NHANES 2009–2018)
Authors: Yan Fengjuan , Zhao Limin , Quan Xiaoqing , Zhu Jialiang
Published: April 2024

Background

Stress hyperglycemia is a physiological response of the body under stress to make adaptive adjustments in response to changes in the internal environment. The stress hyperglycemia ratio (SHR) is a new indicator after adjusting the basal blood glucose level of the population. Previous studies have shown that SHR is associated with poor prognosis in many diseases, such as cardiovascular and cerebrovascular diseases and delirium in elderly patients. However, there are currently no studies on the correlation between SHR and the general U.S. population. The purpose of this study was to examine the association between SHR and adverse outcomes among adults in the United States in general.

Methods

Data on 13,315 follow-up cohorts were extracted from NHANES. The study population was divided into four groups according to quartiles of SHR. The primary outcomes were all-cause mortality and diabetes mellitus mortality. The relationship between SHR and outcomes was explored using restricted cubic splines, COX proportional hazards regression, Kaplan-Meier curves, and mediation effects. SHR is incorporated into eight machine learning algorithms to establish a prediction model and verify the prediction performance.

Results

A total of 13,315 individual data were included in this study. Restricted cubic splines demonstrated a “U-shaped” association between SHR and all-cause mortality and diabetes mellitus mortality, indicating that increasing SHR is associated with an increased risk of adverse events. Compared with lower SHR, higher SHR was significantly associated with an increased risk of all cause mortality and diabetes mellitus mortality (HR > 1, P < 0.05). The mediating effect results showed that the positively mediated variables were segmented neutrophils and aspartate aminotransferase, and the negatively mediated variables were hemoglobin, red blood cell count, albumin, and alanine aminotransferase. The ROC of the eight machine learning algorithm models are XGBoost (0.8688), DT (0.8512), KNN (0.7966), RF (0.8417), Logistic regression (0.8633), ENET (0.8626), SVM (0.8327) and MLP (0.8662).

Conclusion

SHR can be used as a predictor of all cause mortality and diabetes mellitus mortality in the general adult population in the United States. Higher SHR is significantly associated with an increased risk of poor prognosis, especially in those aged < 65 years and in women.
Reference intervals of complete blood count parameters in the adult western Sudanese population
Authors: Mustafa Malak Ibrahim , Ali Ibrahim Abdelrhim , Mohammed Muaath Ahmed , Taha Elmutaz Hussien , Awad Kamal Mohamed , Musa Omer Abdelaziz
Published: April 2024

Background

A complete blood count (CBC) analysis is one of the most common conventional blood tests that physicians frequently prescribe.

The objective

of this study was to determine the reference intervals (RIs) of CBC parameters in the population of healthy adults living in the western Sudan region.

Methods

A cross-sectional study of healthy people residing in the western area of Sudan was carried out. We assessed the CBC RIs in samples taken from 153 individuals using an automated haematology analyser (Sysmex KX-21) and a modified Box–Cox transformation procedure to transform the data into a Gaussian distribution after eliminating outliers using the Dixon method. IBM SPSS Statistics version 25 was used to analyse the data, and t tests were employed to examine variations in the mean CBC parameters according to sex and age. P was considered significant at ≤ 0.05.

Results

Beyond all the other measured values, the only CBC parameters that significantly differed between the sexes were haemoglobin (HGB) and white blood cell (WBC) counts. Women were found to experience more WBC counts than men did. However, they have less HGB RIs.The male participants in our study exhibited lower WBC count RIs, a significantly lower limit, and a greater upper limit of platelet RIs than did the individuals from other nations.

Conclusions

Compared with males, females had higher platelet and WBC counts and lower HGB.
Delirium screening in the emergency department: evaluation and intervention
Authors: Meged-Book Tehilah , Frenkel Reut , Nikonov Anna , Zeldetz Vladimir , Kosto Amit , Schwarzfuchs Dan , Freud Tamar , Press Yan
Published: April 2024

Background

Between 8–17% of older adults, and up to 40% of those arriving from nursing homes, present with delirium upon admission to the Emergency Department (ED). However, this condition often remains undiagnosed by ED medical staff. We investigated the prevalence of delirium among patients aged 65 and older admitted to the ED and assessed the impact of a prospective study aimed at increasing awareness.

Methods

The study was structured into four phases: a "pre-intervention period" (T0); an "awareness period" (T1), during which information about delirium and its diagnosis was disseminated to ED staff; a "screening period" (T2), in which dedicated evaluators screened ED patients aged 65 and older; and a "post-intervention period" (T3), following the departure of the evaluators. Delirium screening was conducted using the Brief Confusion Assessment Method (bCAM) questionnaire.

Results

During the T0 and T1 periods, the rate of delirium diagnosed by ED staff was below 1%. The evaluators identified a delirium rate of 14.9% among the screened older adults during the T2 period, whereas the rate among those assessed by ED staff was between 1.6% and 1.9%. Following the evaluators' departure in the T3 period, the rate of delirium diagnosis decreased to 0.89%.

Conclusions

This study underscores that a significant majority of older adult delirium cases remain undetected by ED staff. Despite efforts to increase awareness, the rate of diagnosis did not significantly improve. While the presence of dedicated delirium evaluators slightly increased the diagnosis rate among patients assessed by ED staff, this rate reverted to pre-intervention levels after the evaluators left. These findings emphasize the necessity of implementing mandatory delirium screening during ED triage and throughout the patient’s stay.
Severe Legionnaires’ disease
Authors: Rello Jordi , Allam Camille , Ruiz-Spinelli Alfonsina , Jarraud Sophie
Published: April 2024

Background

Legionnaires’ disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD.

Results

The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases.

Conclusions

Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed.

Graphical Abstract