bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interstitial Lung Disease Patient Pathway: From Referral To Diagnosis
Authors: Lough Graham , Abdulqawi Rayid , Amanda Gina , Antoniou Katerina , Azuma Arata , Baldi Milind , Bayoumy Ahmed , Behr Jürgen , Bendstrup Elisabeth , Bouros Demosthenes , Brown Kevin , Chaudhuri Nazia , Corte Tamera J. , Cottin Vincent , Crestani Bruno , Flaherty Kevin R. , Glaspole Ian , Kawano-Dourado Leticia , Keane Michael P. , Kolb Martin , Martinez Fernando J. , Molina-Molina Maria , Ojanguren Iñigo , Pearmain Laurence , Raghu Ganesh , Rottoli Paola , Stanel Stefan C. , Tabaj Gabriela , Vancheri Carlo , Varela Brenda , Wang Bonnie , Wells Athol , Rivera-Ortega Pilar
Published: October 2024

Background

Suspected Interstitial Lung Disease (ILD) patients may be referred to an ILD-specialist centre or non-ILD-specialist centre for diagnosis and treatment. Early referral and management of patients at ILD-specialist centres has been shown to improve survival and reduce hospitalisations. The COVID-19 pandemic has affected the ILD patient diagnostic pathway and prompted centres to adapt.

Aims

This study investigates and contrasts ILD patient pathways in ILD-specialist and non-ILD-specialist centres, focusing on referrals, caseloads, diagnostic tools, multi-disciplinary team (MDT) meeting practices, and resource accessibility.

Methods

Conducted as a cross-sectional study, a global self-selecting survey ran from September 2022 to January 2023. Participants included ILD specialists and healthcare professionals (HCPs) from ILD-specialist centres and non-ILD-specialist centres.

Results

Of 363 unique respondents from 64 countries, 259 were from ILD-specialist centres and 104 from non-ILD-specialist centres. ILD centres had better resource availability, exhibiting higher utilisation of diagnostic tests (median: 12 tests), than non-ILD centres (9 tests); and better access to specialist professions attending MDTs (median: 6 professions at meeting) in specialist centres than non-ILD centres (3 professions at meeting). Transitioning to virtual MDTs allowed HCPs from outside of centres to join meetings in nearly 90% of all centres, increasing regular participation in 60% of specialist centres and 72% of non-ILD centres. For treatment of patients, specialist centres had better access to antifibrotic drugs (91%) compared to non-ILD centres (60%).

Conclusions

Diagnostic pathways for ILD patients diverged between specialist centres and non-ILD centres. Disparities in resource and specialist availability existed between centres.
Occurrence and role of Tph cells in various renal diseases
Authors: Ren Junyi , Ma Kuai , Lu Xiangheng , Peng Haoyu , Wang Jia , Nasser Moussa Ide , Liu Chi
Published: October 2024

A new population of peripheral helper T (Tph) cells has been identified and contributed to various autoimmune diseases. Tph cells can secrete interleukin-21 (IL-21), interferon (IFN) and C-X-C motif chemokine ligand 13 (CXCL13) to moderate renal disease. Moreover, Tph cells can congregate in huge numbers and immerse within inflamed tissue. Compared to Tfh cells, Tph cells express high programmed cell death protein 1 (PD-1), major histocompatibility complex II (MHC-II), C-C chemokine receptor 2 (CCR2) and C-C chemokine receptor 5 (CCR5) but often lack expression of the chemokine receptor C-X-C chemokine receptor 5 (CXCR5). They display features distinct from other T cells, which are uniquely poised to promote responses and antibody production of B cells within pathologically inflamed non-lymphoid tissues and a key feature of Tph cells. In this review, we summarize recent findings on the role of Tph cells in chronic kidney disease, acute kidney injury, kidney transplantation and various renal diseases.
Rewriting cellular fate: epigenetic interventions in obesity and cellular programming
Authors: Li Rui-lin , Kang Sheng
Published: October 2024

External constraints, such as development, disease, and environment, can induce changes in epigenomic patterns that may profoundly impact the health trajectory of fetuses and neonates into adulthood, influencing conditions like obesity. Epigenetic modifications encompass processes including DNA methylation, covalent histone modifications, and RNA-mediated regulation. Beyond forward cellular differentiation (cell programming), terminally differentiated cells are reverted to a pluripotent or even totipotent state, that is, cellular reprogramming. Epigenetic modulators facilitate or erase histone and DNA modifications both in vivo and in vitro during programming and reprogramming. Noticeably, obesity is a complex metabolic disorder driven by both genetic and environmental factors. Increasing evidence suggests that epigenetic modifications play a critical role in the regulation of gene expression involved in adipogenesis, energy homeostasis, and metabolic pathways. Hence, we discuss the mechanisms by which epigenetic interventions influence obesity, focusing on DNA methylation, histone modifications, and non-coding RNAs. We also analyze the methodologies that have been pivotal in uncovering these epigenetic regulations, i.e., Large-scale screening has been instrumental in identifying genes and pathways susceptible to epigenetic control, particularly in the context of adipogenesis and metabolic homeostasis; Single-cell RNA sequencing (scRNA-seq) provides a high-resolution view of gene expression patterns at the individual cell level, revealing the heterogeneity and dynamics of epigenetic regulation during cellular differentiation and reprogramming; Chromatin immunoprecipitation (ChIP) assays, focused on candidate genes, have been crucial for characterizing histone modifications and transcription factor binding at specific genomic loci, thereby elucidating the epigenetic mechanisms that govern cellular programming; Somatic cell nuclear transfer (SCNT) and cell fusion techniques have been employed to study the epigenetic reprogramming accompanying cloning and the generation of hybrid cells with pluripotent characteristics, etc. These approaches have been instrumental in identifying specific epigenetic marks and pathways implicated in obesity, providing a foundation for developing targeted therapeutic interventions. Understanding the dynamic interplay between epigenetic regulation and cellular programming is crucial for advancing mechanism and clinical management of obesity.
Shark fin ECG pattern in a patient with acute ascending aortic dissection
Authors: Caccioppola Alessio , Russo Filippo Maria , Molho Enrico , Fargione Lorenzo , Guareschi Alessandro , Colombo Federico , Jachetti Alessandro
Published: October 2024

The ‘shark-fin’ ECG-sign is a rare electrocardiographic pattern seen in ACS, typically associated with poor prognosis. However, its manifestation in acute aortic syndromes remains largely unexplored. Here, we present a case of a patient diagnosed with Ascending Aortic Dissection, who presented to ED with acute chest pain and shark-fin ECG-pattern.
Candidate genes involved in biosynthesis and degradation of the main extracellular matrix polysaccharides of brown algae and their probable evolutionary history
Authors: Mazéas Lisa , Bouguerba-Collin Ahlem , Cock J. Mark , Denoeud France , Godfroy Olivier , Brillet-Guéguen Loraine , Barbeyron Tristan , Lipinska Agnieszka P. , Delage Ludovic , Corre Erwan , Drula Elodie , Henrissat Bernard , Czjzek Mirjam , Terrapon Nicolas , Hervé Cécile
Published: October 2024

Background

Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data.

Results

An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae.

Conclusions

Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.
Influences on the duration and success of out-of-hospital resuscitation of geriatric patients over 80 years of age - a retrospective evaluation
Authors: Heuser Nils , Rupp Dennis , Glass Susanne , Sassen Martin Christian , Morin Astrid , Volberg Christian
Published: October 2024

Background

Society is experiencing an increasing shift in the age distribution and accordingly, increased resuscitation rates of patients over 80 years and older. In 2022, more than 34% of people resuscitated in Germany were older than 80 years, although older age is considered a poor predictor for the outcome of cardiopulmonary resuscitation (CPR). Professional societies provide ethical recommendations on when resuscitation may be considered futile and should be terminated. However, the extent to which these recommendations are implemented is unclear.

Methods

Retrospective evaluation of pre-hospital documentation of out-of-hospital resuscitations in patients ≥ 80 years of age in the period 01/01/2014–12/31/2022 in one German county combined with data of the German Resuscitation Registry. For statistical testing, the significance level was set at p < 0.05.

Results

In total 578 cases were analyzed. Return of spontaneous circulation (ROSC): 26% (n = 148). Survival to discharge: 6.1% (n = 35). Median CPR duration: 17 min (10–28 min). The older the patients were, the worse the survival rate (p = 0.05) and the shorter the time to termination (p < 0.0001). No patient over 90 years of age was discharged alive. Resuscitation was also significantly shorter until termination with poorer ASA (American Society of Anesthesiologists) score (p < 0.001). Residents resuscitated significantly longer than specialists (p = 0.02). In surviving patients, there was a significant correlation between short CPR duration and good cerebral performance category (CPC) value: Median CPC1/2 = 5 min [3–10 min] vs. CPC 3/4 = 18 min [10–21 min]; p = 0.01.

Interpretation

Old age and poor health status is associated with shorter CPR duration until termination and older age is associated with poorer prognosis in out-of-hospital cardiac arrest (OHCA) concerning the possibility of return of spontaneous circulation (ROSC) and survival. A short resuscitation time is associated with a better CPC value. Therefore, when resuscitating patients over 80 years of age, even greater care should be taken to ensure that reversible causes are quickly corrected in order to achieve a ROSC and a good neurological outcome. Alternatively, resuscitation should be terminated promptly, as good survival can no longer be guaranteed. Resuscitation lasting more than 20 min should be avoided in any case, in line with the termination of resuscitation (ToR) criteria.
Is interval chemotherapy safe and does it improve the outcome of patients with colorectal liver metastases undergoing multimodal two-stage hepatectomy? – A systematic literature review
Authors: Raschzok Nathanael , Moosburner Simon , Blank Moritz , Krenzien Felix , Lurje Georg , Schöning Wenzel , Sauer Igor M. , Pratschke Johann , Modest Dominik P. , Kurreck Annika
Published: October 2024

Background

Multimodal two-stage hepatectomy (mTSH) is used in patients with bilobar colorectal liver metastases (CRLM) that cannot be treated with one surgical procedure due to insufficient future liver remnant. Interval chemotherapy has been proposed to improve disease control in CRLM patients undergoing mTSH. We here present a narrative review of clinical studies on mTSH including the use of interval chemotherapy in patients with CRLM.

Methods

A systematic literature search of the PubMed databases as well as the ClinicalTrials.gov registry was performed.

Results

The use of interval chemotherapy during mTSH was reported in 23 studies and applied in 595 out of 1,461 patients with CRLM. Two studies report on the actual effects of this treatment, one study describes a trend towards improved disease progression rate. No serious adverse events caused by interval chemotherapy were observed. There is currently no randomized clinical trial investigating the efficacy and safety of interval chemotherapy during mTSH.

Conclusion

The currently available data indicate that interval chemotherapy does neither impair liver hypertrophy during mTSH nor cause procedure-associated complications in patients with CRLM. Results from randomized clinical trials on the potential positive effect on disease control are not yet available.
Prognostic value of myositis-specific antibodies in patients with idiopathic interstitial pneumonia
Authors: Wakabayashi Hiroki , Iwasaki Kotaro , Murakami Yu , Takashima Kenta , Kaneko Kaichi , Matsuzawa Yasuo
Published: October 2024

Background

Patients with idiopathic interstitial pneumonia (IIP) often exhibit positivity for myositis-specific antibodies (MSA). However, the significance of this finding remains unclear. In this study, we investigated the association of MSA with the prognosis and risk of acute exacerbation in patients with IIP.

Methods

We retrospectively reviewed the medical records of patients with IIP and examined the effect of each MSA subtype on survival and acute exacerbation.

Results

Of 240 patients with IIP, 48 (20%) exhibited positivity for MSA. The MSA subtypes included: PL-7 (antithreonyl; n = 16, 6.7%); signal recognition particle (n = 13, 5.4%); PL-12 (antialanyl; n = 9, 3.8%); Mi-2 (n = 8, 3.3%); OJ (anti-isoleucyl; n = 7, 2.9%). During the 382 days (382 ± 281 days) of observation, 32 (13%) patients expired, and 27 (11%) experienced an acute exacerbation. Cox proportional hazards regression analysis demonstrated that age at the initial visit (hazard ratio [HR]: 1.072; 95% confidence interval [CI]: 1.017–1.131; P = 0.01), PL-7 (HR: 4.785; 95% CI: 1.528–14.925; P = 0.007), and PL-12 (HR: 3.922; 95% CI: 1.198–12.82; P = 0.024) were independent predictors of survival time. PL-7 (HR: 3.268; 95% CI: 1.064–10; P = 0.039) and PL-12 (HR: 5.747; 95% CI: 1.894–7.544; P = 0.002) were independent predictors of time from first visit to acute exacerbation.

Conclusion

Detecting MSA in patients with interstitial lung disease may be useful in predicting prognosis and providing a rationale for intensive treatment.
Robotic assisted simple prostatectomy mitigates perioperative morbidity compared to open simple prostatectomy - a single institution report
Authors: Larsen Magnus , Giske Anneli , Roaldsen Marius , Gullan Dag , Aarsaether Erling
Published: October 2024

Background

According to the guidelines of the European Association of Urology, open simple prostatectomy should be offered to men with a prostate size exceeding 80 mL suffering from moderate to severe LUTS in the absence of a transurethral enucleation technique. However, open simple prostatectomy is associated with complications such as bleeding, blood transfusions and increased length of stay compared to minimally invasive procedures. The aim of the study was to compare perioperative data from the first cases of robotic assisted simple prostatectomy (RASP) to that of patients subjected to open simple prostatectomy (OSP) at our department.

Methods

The patients were identified by a search for the respective procedure codes. In the OSP group enucleation of the adenoma was performed through the prostatic capsule (Millin procedure), while access to the adenoma was gained through the bladder in the RASP group. Complications were scored according to the Clavien-Dindo classification system.

Results

27 patients who underwent OSP were retrospectively identified and compared to the first 26 patients who were subjected to RASP. The groups were similar with respect to age, body mass index and ASA score. Operative time was significantly shorter in the OSP group compared to the RASP group. Bleeding volume, drop in postoperative hemoglobin and the number of blood transfusions were all significantly higher in the OSP group compared to the RASP group. Average length of stay was 5.5 (2–18) days in the OSP group compared to 1.6 (1–5) days in the RASP group (p < 0.001). The number of postoperative complications, Clavien-Dindo ≥ 2, were significantly higher in the OSP group (11) compared to the RASP group (none, p < 0.001).

Conclusions

The introduction of robotic assisted simple prostatectomy reduced perioperative morbidity at our department.
HbA1c comparable to fasting glucose in the external validation of the African Diabetes Risk Score and other established risk prediction models in Black South Africans
Authors: Royce Nicola , Cronjé Héléne T , Kengne André P , Kruger Herculina S , Dolman-Macleod Robin C , Pieters Marlien
Published: October 2024

Background

The use of non-invasive risk scores to detect undiagnosed type 2 diabetes (T2D) ensures the restriction of invasive and costly blood tests to those most likely to be diagnosed with the disease. This study assessed and compared the performance of the African Diabetes Risk Score (ADRS) with three other diabetes risk prediction models for identifying screen-detected diabetes based on fasting plasma glucose (FPG) or glycated haemoglobin (HBA1c).

Methods

Age, sex, waist circumference, body mass index, blood pressure, history of diabetes and physical activity levels from the SA-NW-PURE study were used to externally validate the ADRS and other established risk prediction models. Discrimination was assessed and compared using C-statistics and nonparametric methods. Calibration was assessed using calibration plots, before and after recalibration.

Results

Nine hundred and thirty-seven participants were included; 14% had prevalent undiagnosed T2D according to FPG and 26% according to HbA1c. Discrimination was acceptable and was mostly similar between models for both diagnostic measures. The C-statistics for diagnosis by FPG ranged from 0.69 for the Simplified FINDRISC model to 0.77 for the ADRS model and 0.77 for the Simplified FINDRISC model to 0.79 for the ADRS model for diagnosis by HbA1c. Calibration ranged from acceptable to good, though over- and underestimation were present. All models improved significantly following recalibration.

Conclusions

The models performed comparably, with the ADRS offering a non-invasive way to identify up to 79% of cases. Based on its ease of use and performance, the ADRS is recommended for screening for T2D in certain Black population groups in South Africa. HbA1c as a means of diagnosis also showed comparable performance with FPG. Therefore, further validation studies can potentially use HbA1c as the standard to compare to.
Nurses’ experience of nasogastric tube feeding under restraint for Anorexia Nervosa in a psychiatric hospital
Authors: Brinchmann Berit Støre , Ludvigsen Mette Spliid , Godskesen Tove
Published: October 2024

Background

Anorexia nervosa is a complex mental disorder that has severe physical and psychological consequences, often requiring hospitalisation, and in the most severe cases, patients receive coercive treatment. Among the various nursing tasks associated with encountering these patients, the administration of nasogastric tube feeding under restraint stands out. It is crucial to recognise and address the unique practical and ethical challenges nurses face when caring for adults struggling with severe anorexia nervosa. The aim of the study was to gain a deeper understanding of registered nurses’ experience of nasogastric tube feeding under restraint in hospitalised patients with severe anorexia nervosa.

Methods

A naturalistic design guided this study. Narrative interview data were analysed using reflexive thematic analysis. The participants were twelve registered nurses recruited from an inpatient ward for adult patients with an eating disorder in a Norwegian psychiatric hospital.

Results

Three main themes were developed: providing good nursing care during coercive treatment; having ethical concerns about nasogastric tube feeding under restraint when the patient reaches a body mass index that is not immediately life-threatening; and having concerns about involving personnel from another ward in the nasogastric tube feeding under restraint procedure.

Conclusions

Nurses find nasogastric tube feeding under restraint to be part of life-saving nursing for patients with severe anorexia nervosa. It raises ethical concerns, especially with patients with a body mass index that is no longer life-threatening. Our results demonstrate the vulnerability of nurses as well as the difficulties and ethical dilemmas of nursing during nasogastric tube feeding under restraint.
Rapid evolution of mitochondrion-related genes in haplodiploid arthropods
Authors: Li Yiyuan , Thomas Gregg W. C. , Richards Stephen , Waterhouse Robert M. , Zhou Xin , Pfrender Michael E.
Published: October 2024

Background

Mitochondrial genes and nuclear genes cooperate closely to maintain the functions of mitochondria, especially in the oxidative phosphorylation (OXPHOS) pathway. However, mitochondrial genes among arthropod lineages have dramatic evolutionary rate differences. Haplodiploid arthropods often show fast-evolving mitochondrial genes. One hypothesis predicts that the small effective population size of haplodiploid species could enhance the effect of genetic drift leading to higher substitution rates in mitochondrial and nuclear genes. Alternatively, positive selection or compensatory changes in nuclear OXPHOS genes could lead to the fast-evolving mitochondrial genes. However, due to the limited number of arthropod genomes, the rates of evolution for nuclear genes in haplodiploid species, besides hymenopterans, are largely unknown. To test these hypotheses, we used data from 76 arthropod genomes, including 5 independently evolved haplodiploid lineages, to estimate the evolutionary rates and patterns of gene family turnover of mitochondrial and nuclear genes.

Results

We show that five haplodiploid lineages tested here have fast-evolving mitochondrial genes and fast-evolving nuclear genes related to mitochondrial functions, while nuclear genes not related to mitochondrion showed no significant evolutionary rate differences. Among hymenopterans, bees and ants show faster rates of molecular evolution in mitochondrial genes and mitochondrion-related nuclear genes than sawflies and wasps. With genome data, we also find gene family expansions and contractions in mitochondrion-related genes of bees and ants.

Conclusions

Our results reject the small population size hypothesis in haplodiploid species. A combination of positive selection and compensatory changes could lead to the observed patterns in haplodiploid species. The elevated evolutionary rates in OXPHOS complex 2 genes of bees and ants suggest a unique evolutionary history of social hymenopterans.
Comparative evaluation of the extracellular production of a polyethylene terephthalate degrading cutinase by Corynebacterium glutamicum and leaky Escherichia coli in batch and fed-batch processes
Authors: Fritzsche Stefanie , Hübner Holger , Oldiges Marco , Castiglione Kathrin
Published: October 2024

Background

With a growing global population, the generation of plastic waste and the depletion of fossil resources are major concerns that need to be addressed by developing sustainable and efficient plastic recycling methods. Biocatalytic recycling is emerging as a promising ecological alternative to conventional processes, particularly in the recycling of polyethylene terephthalate (PET). However, cost-effective production of the involved biocatalyst is essential for the transition of enzymatic PET recycling to a widely used industrial technology. Extracellular enzyme production using established organisms such as Escherichia coli or Corynebacterium glutamicum offers a promising way to reduce downstream processing costs.

Results

In this study, we compared extracellular recombinant protein production by classical secretion in C. glutamicum and by membrane leakage in E. coli. A superior extracellular release of the cutinase ICCGDAQI was observed with E. coli in batch and fed-batch processes on a litre-scale. This phenomenon in E. coli, in the absence of a signal peptide, might be associated with membrane-destabilizing catalytic properties of the expressed cutinase. Optimisations regarding induction, expression temperature and duration as well as carbon source significantly enhanced extracellular cutinase activity. In particular, in fed-batch cultivation of E. coli at 30 °C with lactose as carbon source and inducer, a remarkable extracellular activity (137 U mL−1) and cutinase titre (660 mg L−1) were achieved after 48 h. Literature values obtained with other secretory organisms, such as Bacillus subtilis or Komagataella phaffii were clearly outperformed. The extracellular ICCGDAQI produced showed high efficacy in the hydrolysis of PET textile fibres, either chromatographically purified or unpurified as culture supernatant. In less than 18 h, 10 g L−1 substrate was hydrolysed using supernatant containing 3 mg cutinase ICCGDAQI at 70 °C, pH 9 with terephthalic acid yields of up to 97.8%.

Conclusion

Extracellular production can reduce the cost of recombinant proteins by simplifying downstream processing. In the case of the PET-hydrolysing cutinase ICCGDAQI, it was even possible to avoid chromatographic purification and still achieve efficient PET hydrolysis. With such production approaches and their further optimisation, enzymatic recycling of PET can contribute to a more efficient and environmentally friendly solution to the industrial recycling of plastics in the future.
A global mathematical model of climatic suitability for Plasmodium falciparum malaria
Authors: Brown Owen , Flegg Jennifer A. , Weiss Daniel J. , Golding Nick
Published: October 2024

Climatic conditions are a key determinant of malaria transmission intensity, through their impacts on both the parasite and its mosquito vectors. Mathematical models relating climatic conditions to malaria transmission can be used to develop spatial maps of climatic suitability for malaria. These maps underpin efforts to quantify the distribution and burden of malaria in humans, enabling improved monitoring and control. Previous work has developed mathematical models and global maps for the suitability of temperature for malaria transmission. In this paper, existing temperature-based models are extended to include two other important bioclimatic factors: humidity and rainfall. This model is combined with fine spatial resolution climatic data to produce a more biologically-realistic global map of climatic suitability for Plasmodium falciparum malaria. The climatic suitability index developed corresponds more closely than previous temperature suitability indices with the global distribution of P. falciparum malaria. There is weak agreement between the Malaria Atlas Project estimates of P. falciparum prevalence in Africa and the estimates of suitability solely based on temperature (Spearman Correlation coefficient of $$\rho = 0.24$$

ρ
=
0.24

). The addition of humidity and then rainfall improves the comparison ($$\rho = 0.62$$

ρ
=
0.62

when humidity added; $$\rho =0.70$$

ρ
=
0.70

when both humidity and rainfall added). By incorporating the impacts of humidity and rainfall, this model identifies arid regions that are not climatically suitable for transmission of P. falciparum malaria. Incorporation of this improved index of climatic suitability into geospatial models can improve global estimates of malaria prevalence and transmission intensity.
Mutational analysis differentiating sporadic carcinomas from colitis-associated colorectal carcinomas
Authors: Dregelies Theresa , Haumaier Franziska , Sterlacci William , Backert Steffen , Vieth Michael
Published: October 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that is associated with increased risk of developing colitis-associated carcinoma (CAC). The genetic profile of CACs is fairly similar to the sporadic colorectal carcinomas (sCRCs), although showing certain differences in the timing and sequence of alterations that contribute to carcinogenesis. Also, both cancer types typically show a strong histological resemblance, which complicates the pathologists’ diagnosis. Due to the different clinical consequences, it is of utmost importance to categorize the corresponding cancer type correctly.

Methods

In this study, we determined the mutation profiles of 64 CACs and sCRCs in the hotspot regions of 50 cancer-associated genes and compared them to 29 controls to identify genetic gene variants that can facilitate the pathologists’ diagnosis. Pearson Chi-Square or Fisher’s exact tests were used for statistical analyses.

Results

We found that sCRCs tend to mutate more frequently in APC and PIK3CA genes than CACs and that mainly males were affected. Our CAC cohort identified the KRAS G12D mutation as group-specific variant that was not detected in the sCRCs. When separating conventional from non-conventional CACs, it was discovered that the conventional type shows significantly more mutations for ATM.

Conclusions

Taken together, our data highlights genetic differences between sCRC and CAC and enables the possibility to utilize specific gene alterations to support the pathologist’s diagnosis.
Infrared spectroscopy as a new approach for early fabry disease screening: a pilot study
Authors: Barretto Carolina Teles , Nascimento Márcia Helena Cassago , Brun Bruna Ferro , da Silva Tiago Barcelos , Dias Pedro Augusto Costa , Silva Cassiano Augusto Braga , Singh Maneesh N. , Martin Francis L. , Filgueiras Paulo Roberto , Romão Wanderson , Campos Luciene Cristina Gastalho , Barauna Valerio Garrone
Published: October 2024

Background

Fabry disease (FD) is a rare X-linked lysosomal storage disorder marked by alpha-galactosidase-A (α-Gal A) deficiency, caused by pathogenic mutations in the GLA gene, resulting in the accumulation of glycosphingolipids within lysosomes. The current screening test relies on measuring α-Gal A activity. However, this approach is limited to males. Infrared (IR) spectroscopy is a technique that can generate fingerprint spectra of a biofluid’s molecular composition and has been successfully applied to screen numerous diseases. Herein, we investigate the discriminating vibration profile of plasma chemical bonds in patients with FD using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy.

Results

The Fabry disease group (n = 47) and the healthy control group (n = 52) recruited were age-matched (39.2 ± 16.9 and 36.7 ± 10.9 years, respectively), and females were predominant in both groups (59.6% and 65.4%, respectively). All patients had the classic phenotype (100%), and no late-onset phenotype was detected. A generated partial least squares discriminant analysis (PLS-DA) classification model, independent of gender, allowed differentiation of samples from FD vs. control groups, reaching 100% sensitivity, specificity and accuracy.

Conclusion

ATR-FTIR spectroscopy harnessed to pattern recognition algorithms can distinguish between FD patients and healthy control participants, offering the potential of a fast and inexpensive screening test.
Transipedia.org: k-mer-based exploration of large RNA sequencing datasets and application to cancer data
Authors: Bessière Chloé , Xue Haoliang , Guibert Benoit , Boureux Anthony , Rufflé Florence , Viot Julien , Chikhi Rayan , Salson Mikaël , Marchet Camille , Commes Thérèse , Gautheret Daniel
Published: October 2024

Indexing techniques relying on k-mers have proven effective in searching for RNA sequences across thousands of RNA-seq libraries, but without enabling direct RNA quantification. We show here that arbitrary RNA sequences can be quantified in seconds through their decomposition into k-mers, with a precision akin to that of conventional RNA quantification methods. Using an index of the Cancer Cell Line Encyclopedia (CCLE) collection consisting of 1019 RNA-seq samples, we show that k-mer indexing offers a powerful means to reveal non-reference sequences, and variant RNAs induced by specific gene alterations, for instance in splicing factors.
Simple simultaneous analysis of various cardiovascular drug mixtures with vincamine: comparative eco-friendly assessment
Authors: Mourad Sara S. , Barary Magda A. , El-Yazbi Amira F.
Published: October 2024

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.
Impact of virtual reality hypnosedation on perioperative pain and anxiety in port implantation under local anesthesia: a randomized controlled pilot trial (VIP Trial)
Authors: Steinkraus Kira C. , Feldmann Hannah , Hunold Lisa S. , Graf Sandra , Dörr-Harim Colette , Nasir Nadir , Michalski Christoph W. , Hüttner Felix J.
Published: October 2024

Background

This monocentric randomized controlled pilot trial investigates the impact of virtual reality (VR) hypnosedation on perioperative anxiety, pain, patient satisfaction, and medication usage during port implantation under local anesthesia.

Methods

A total of 120 patients undergoing elective port implantation between January 2022 and August 2023 were enrolled and randomized in a 1:1 ratio to either a VR hypnosedation group or a control group. The VR group used a commercially available VR headset with the HypnoVR application, providing various environments, musical backgrounds, and a guiding voice, while the control group underwent the procedure without VR. Patients with ASA > 3, chronic pain, cognitive issues, and contraindications against VR use were excluded. The main outcomes measured were perioperative pain and anxiety scores, with secondary outcomes including perioperative medication usage. Due to the nature of the interventions, blinding of patients and physicians was not feasible. Statistical analysis was primarily descriptive and exploratory, focusing on estimating effect sizes for future trials.

Results

The study found no significant differences in immediate postoperative pain with 1.43 ± 1.63 vs. 1.6 ± 2.05 (p = 0.62) or anxiety scores 30.65 ± 9.13 vs. 31.78 ± 13.34 (p = 0.60) between the no VR and VR group, respectively. Additionally, there was a trend to less usage of certain medications, particularly remifentanil (mean dose of 200 mg vs. 100 mg (p = 0.12)) and novaminsulfon (mean dose of 1250 mg vs. 900 mg (p = 0.26)) in the VR group vs. no VR group, respectively. However, these differences were not statistically significant and therefore no definitive conclusions can be drawn regarding medication usage based on this data.

Conclusion

While VR hypnosedation did not significantly reduce perioperative pain or anxiety in this pilot trial, the observed trends in reduced medication usage suggest potential benefits. These findings warrant further investigation in larger, confirmatory trials to better understand the role of VR in enhancing patient comfort and potentially reducing reliance on pharmacological interventions during surgical procedures.

Trial registration

German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275–4995.
How to interpret Jiangnan gardens: a study of the spatial layout of Jiangnan gardens from the perspective of fractal geometry
Authors: Sun Ce , Jiang Zhenyu , Yu Bingqin
Published: October 2024

This study contributes to design studies by offering a novel approach to understanding the spatial layout of Jiangnan gardens through the lens of fractal geometry. Analyzing 106 gardens, we found that the ideal fractal dimension range for Jiangnan gardens is 1.148 ~ 1.276, with gardens in the 2500 ~ 7200 m2 range exhibiting the highest complexity (1.238 ~ 1.276). Additionally, for gardens ranging from 2500  ~ 20,000 m2, the maximum spacious space area stabilizes, no longer expanding indefinitely with overall area. This suggests a design principle of spatial proportion and balance. By quantifying spatial complexity and the contrast between spacious and profund spaces, the study provides a new method for evaluating garden design and can help students and designers better apply the principles of Jiangnan garden design.
A review of geopolymer binder as a grouting material
Authors: Sierra Karla , An Jinwoo , Shamet Ryan , Chen Jiannan , Kim Yong Je , Nam Boo Hyun , Park Philip
Published: October 2024

The utilization of geopolymer as a grouting material has gained significant attention in research and construction applications. Geopolymer grout is a type of binding material that differs from traditional grouts, typically based on Portland cement. Researchers have explored its effectiveness and potential applications in grouting processes, considering its unique properties and characteristics. In this paper, various studies employing and utilizing geopolymer as a grouting material are reviewed. The emphasis is on mixture design of geopolymer grout, physical property, chemical composition of geopolymer grout, rheological behavior of geopolymer grout such as yield stress (in case of Bingham fluid) and viscosity, and engineering properties such as compressive strength, expansion, shrinkage, etc.
A proof-of-concept study of a prototype needle that mitigates intraocular pressure rise following intravitreal injection
Authors: Sverstad Alexander , Kristianslund Olav , Petrovski Goran , Moe Morten Carstens , Jørstad Øystein Kalsnes
Published: October 2024

Purpose

To determine the feasibility of a prototype needle that enhances vitreous reflux (VR) to control intraocular pressure (IOP) in intravitreal injection (IVI).

Methods

We created an eye model to compare IVI using a standard 30-G needle with four different versions of a 30-G prototype needle with one to four surface grooves that enhanced VR. We injected 50, 70, and 100 µl saline through porcine sclera or 460-µm-thick rubber and measured the peak and 3-second pressure before we extracted the needle and measured the 10-second pressure.

Results

50-µl injection through sclera with the standard needle resulted in mean (SD) pressure of 58.6 (3.8) mmHg at peak, 52.8 (4.7) mmHg at 3 s, and 39.6 (18.0) mmHg at 10 s. The prototype needle lowered the pressure; four grooves resulted in mean (SD) pressure of 29.4 (5.6) mmHg at peak, 22.0 (3.7) mmHg at 3 s, and 7.2 (6.6) mmHg at 10 s. 70-µl and 100-µl injections through sclera with the standard needle resulted in mean (SD) pressure of 68.8 (3.6) and 86.0 (6.0) mmHg at peak. Similar to 50-µl injection, the prototype needle lowered the pressure for 70-µl and 100-µl injections. At 10 s, we observed varying leakage at the injection site for sclera but not for rubber.

Conclusions

The study provides proof of concept for a needle design for which surface grooves enhance VR and counteract the effect of IVI on IOP. The safety and efficacy of the prototype needle must be studied further in a clinical trial.
Anesthetic management of a patient with mandibular hypoplasia, deafness, progeroid features, lipodystrophy syndrome: a case report
Authors: Sekiguchi Ryo , Kinoshita Michiko , Sakai Yoko , Tanaka Katsuya
Published: October 2024

Background

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder that presents unique challenges for anesthetic management due to its multisystemic manifestations. This report outlines the anesthetic considerations for MDPL patients based on our case experience.

Case presentation

A 15-year-old male with MDPL syndrome underwent testicular extraction under general anesthesia. Insertion of a peripheral venous catheter was challenging due to scleroderma-like skin. Although the facial features of MDPL syndrome suggested a difficult airway, intubation with a McGrath™ Mac video laryngoscope was successful. Despite MDPL syndrome’s association with hypertriglyceridemia due to lipodystrophy, this patient’s triglyceride levels were normal. Thiamylal and sevoflurane were used without issues such as delayed emergence from anesthesia.

Conclusions

MDPL syndrome requires careful preoperative assessment and tailored anesthetic management due to potential airway challenges arising from its distinctive facial features and the possibility of altered anesthetic pharmacokinetics associated with lipodystrophy.
Efficient gene editing with an Arg-tRNA promoter-driven CRISPR/Cas9 in the rice blast fungus Pyricularia oryzae
Authors: Wang Rui-Jin , Zhao Jianhui , Bhadauria Vijai , Peng You-Liang
Published: October 2024

CRISPR/Cas9 technology has been widely adopted for genome editing in a wide range of organisms, including many fungi. Pyricularia oryzae is a filamentous fungal pathogen that causes the devastating rice blast disease. However, an efficient and cost-effective CRISPR/Cas9 system for the rice blast fungus has yet to be established. Here, we report an 84-bp arginyl (Arg)-tRNA promoter-driven CRISPR/Cas9 system, which enables efficient and cost-effective gene editing in P. oryzae. Preliminary screening of three tRNAs from the 179 predicted tRNAs in P. oryzae showed that two Arg-tRNA CRISPR/Cas9 cassettes reproducibly generated MoB56 disruption efficiently. Further, five genes located on distinct chromosomes, including two previously uncharacterized genes, were randomly picked up to test the efficiency of the Mo_tRNAArg24-gRNA-Cas9 cassette. Ppg1 is a gene essential to the pathogenicity and important for mycelial growth and conidiation of P. oryzae, which is located at chromosome 2 and exhibited a relatively low gene replacement rate (< 1/500) by the traditional gene replacement approach. By using the Mo_tRNAArg24-gRNA-Cas9 cassette, Ppg1 gene disruption rate was increased up to 75.9%. In addition, Bip2, an uncharacterized genes located close to the centromere of chromosome 4, was disrupted at 66.7%. For all the five tested genes, our Mo_tRNAArg24-gRNA-Cas9 cassette showed high gene disruption efficiency in P. oryzae, ranging from 66.7% to 100%. Importantly, it rarely induces Cas9 toxicity to P. oryzae. The Mo_tRNAArg24-gRNA-Cas9 cassette described in this study can be adopted as an alternative for functional genomics study in P. oryzae.
The third-generation anticoagulants: factors XI, XII, and XIII inhibitors
Authors: Prajapathi Sudesh , Pradhan Akshyaya , Mohta Aditi , Sethi Rishi
Published: October 2024

Background

Arterial or venous thromboembolic events are responsible for one-fourth of all deaths worldwide. Anticoagulants are the mainstay for the prevention and treatment of venous thromboembolic events (VTE). Heparin and vitamin K antagonists were the first non-specific medications used in anticoagulant therapy, followed by safer alternatives, such as fondaparinux, argatroban, and direct oral anticoagulants. However, the latter bear the risk of potentially lethal internal bleeding. Novel drugs inhibiting various coagulation factors, such as factors XIa, XIIa, and XIIIa, appear to have a lesser risk of bleeding and are in the spotlight. This review aims to consolidate findings from published clinical trials of newer drugs inhibiting factors XIa, XIIa, and XIIIa.

Main body

Factor XI inhibitors have been researched more extensively as compared to factor XII and factor XIII inhibitors. Phase 2 study results of factor XI inhibitors indicated their superiority over enoxaparin for reduction of VTE incidence and better safety profile in terms of bleeding. Factor XII inhibitors also hold the promise of lowering the risk of bleeding, as indicated in animal studies. Further human studies would ensure their safety and applicability in the human population. Numerous laboratory researches have revealed, the potent antithrombotic profile of factor XIII inhibition with limited bleeding risks.

Conclusion

Larger statistically powered studies could supplement data to establish the role of FXI inhibitors in the prevention of both arterial and venous thromboembolic events in high-risk populations. While early results of factor XII and factor XIII inhibitors look promising, they still have a long road ahead before their therapeutic efficacy in humans is established.