This study aimed to assess the effectiveness of nurse-led interventions in managing leprosy due to a shortage of dermatologists and other healthcare professionals.

A total of 100 leprosy patients were divided into experimental (n=50) and control groups (n=50). The intervention included face-to-face counseling by a trained nurse, motivational videos and exercise demonstrations. The control group received standard care. The primary outcome of interest was treatment adherence (Adherence to Refills and Medications Scale); other assessed outcomes included changes in perceived stigma (Stigma Assessment and Reduction of Impact scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder seven-item) and quality of life (WHO QOL-BREF Scale) from baseline to week 8.

The intervention group had better treatment adherence (p<0.001). At baseline, moderately severe and severe depression prevalence was 18% and 28%, respectively, and anxiety was 25%, with no intergroup differences. Anxiety significantly decreased in the intervention group (p<0.001), but depression remained similar (p=0.291). Perceived stigma improved notably, especially in disclosure of concern (p<0.001), internal stigma (p<0.001) and anticipated stigma (p<0.001). Quality of life scores improved in the intervention group vs controls.

Nurse-led interventions effectively enhanced quality of life and treatment adherence and reduced anxiety, depression and perceived stigma among leprosy patients. The study recommends strengthening the capacity of nurses for active involvement in leprosy care.

It is well-documented that using immunosuppressive drugs such as corticosteroids or cytokine blockers in treating coronavirus disease 2019 (COVID-19) increases the risk of co-infections. Here we systematically summarized the cases of COVID-19-associated parasitic infections (CAPIs) in Iran.

From 19 February 2020 to 10 May 2023, all studies on Iranian patients suffering from CAPIs were collected from several databases using a systematic search strategy.

Of 540 records, 11 studies remained for data extraction. In this research, most of the studies were related to Lophomonas and Toxoplasma. Of 411 cases of CAPIs, toxoplasmosis (385 [93.7%]) had the highest rate of infection among Iranian patients, followed by blastocystosis (15 [3.6%]), fascioliasis (4 [0.97%]), leishmaniasis (3 [0.7%]), lophomoniasis (3 [0.7%]) and strongyloidiasis (1 [0.2%]). In general, Blastocystis enhanced diarrhoea in patients with COVID-19. Lophomonas, Toxoplasma and Strongyloides increased the severity of COVID-19, but Fasciola decreased its intensity. Patients with a history of cutaneous leishmaniasis showed mild symptoms of COVID-19. Also, patients with a prior history of hydatid cysts were not affected by COVID-19.

Due to the similar symptoms of some parasitic diseases and COVID-19 and immunosuppressive treatment regimens in these patients that may cause the reactivation or recurrence of parasitic infections, early diagnosis and treatment are required.

Aberrant long noncoding RNAs just proximal to Xist (lncRNA JPX) expression levels have been detected in multiple tumors. However, whether JPX is involved in melanoma progression remains unclear. Our study showed that JPX expression is significantly increased in melanoma tissues and cell lines. To clarify the effect of JPX on cutaneous melanoma, we successfully generated JPX-overexpressing or JPX-knockdown A375 and A2058 cells. CCK-8, colony formation EdU, Transwell, and cell-cycle phase assays were performed, and subcutaneously implanted tumor models were used to determine the function of JPX in cutaneous melanoma. The results showed that JPX knockdown reduced the proliferation and migration of malignant melanoma cells both in vitro and in vivo. To further elucidate the molecular mechanism of JPX-induced cutaneous melanoma deterioration, we performed RNA pull-down, RNA immunoprecipitation, coimmunoprecipitation, Western blot, and RNA-sequence analyses. JPX can directly interact with YTHDF2 and impede the protection of YTHDF2 from ubiquitin-specific protease 10 (USP10), which promotes its deubiquitination. Thus, JPX decreases protein stability and promotes the degradation of YTHDF2, thereby stabilizing BMP2 mRNA and activating AKT phosphorylation. Overall, our study revealed a novel effect of JPX on YTHDF2 ubiquitination, suggesting the possibility of blocking the JPX/USP10/YTHDF2/BMP2 axis as a prospective therapeutic approach for cutaneous melanoma.

This study highlights the ubiquitination effect of USP10 and JPX on YTHDF2 in cutaneous melanoma, and proposes that the JPX/USP10/YTHDF2/BMP2 axis may be a prospective therapeutic target for cutaneous melanoma.

The genus Acanthamoeba is reported from various environmental sources and can cause multiple complications, including chronic amoebic aeratitis and amoebic granulomatous encephalitis. This study investigated the presence and genotyping of Acanthamoeba in the soil of parks and patients with malignancies referred to health centers in Zanjan city, Iran.

In this cross-sectional study, 200 soil samples were collected from amusement parks in Zanjan city from September 2017 to May 2018. Samples were cultured on 1.5% non-nutrient agar, and the Acanthamoeba genus was identified using the morphological method. PCR was performed on all positive environmental samples, and six microscopically positive clinical samples belonged to our previous study. DNA sequencing of 18S rRNA was performed to analyze the genetic pattern of some PCR-positive isolates.

Microscopic results showed that 96 (48%) soil samples were positive. PCR confirmed all positive cases of clinical samples and 84 soil samples. Out of the PCR-positive samples, 20 soil samples and five clinical samples were sequenced successfully. All soil isolates belonged to the T4 genotype, and three and two clinical samples belonged to T4 and T5 genotypes, respectively.

: The presence of Acanthamoeba in both the environment and clinical samples of Zanjan city suggests paying greater attention to the infections caused by it.

Accurate predictions are commonly taken as a hallmark of strong scientific understanding. Yet, we do not seem capable today of making many accurate predictions about biological speciation. Why? What limits predictability in general, what exactly is the function and value of predictions, and how might we go about predicting new species? Inspired by an orrery used to explain solar eclipses, we address these questions with a thought experiment in which we conceive an evolutionary speciation machine generating new species. This experiment highlights complexity, chance, and speciation pluralism as the three fundamental challenges for predicting speciation. It also illustrates the methodological value of predictions in testing and improving conceptual models. We then outline how we might move from the hypothetical speciation machine to a predictive standard model of speciation. Operationalizing, testing, and refining this model will require a concerted shift to large-scale, integrative, and interdisciplinary efforts across the tree of life. This endeavor, paired with technological advances, may reveal apparently stochastic processes to be deterministic, and promises to expand the breadth and depth of our understanding of speciation and more generally, of evolution.

No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterized fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies.

We undertook immunohistochemistry, metabolic, signalling pathway and epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/NSCD fibroblasts were cultured with TGFβ and valproic acid [VPA].

Stricturing CD was characterized by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFβ stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appeared 'metabolically primed' and responded more strongly to both TGFβ and VPA. Treatment with VPA revealed TGFβ-dependent and TGFβ-independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters.

Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype and metabolic priming characterize SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFβ-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis.

Financial toxicity is associated with worse cancer outcomes, including lower survival.

To characterize the prevalence of, and patient risk factors for, financial toxicity among gynecologic oncology patients in a multi-site health system.

We identified patients seen in University of Pennsylvania gynecologic oncology practices between January 2020 and February 2022 with a patient portal account. We sent a survey to all alive patients twice between March and April 2022, including the 11-item Comprehensive Score for Financial Toxicity (COST) tool. We compared differences between patients reporting high (COST score <26) and low financial toxicity (COST score ≥26) in Χ2 and regression analyses.

Of 8239 patients, 6925 had a portal account, and 498 completed the survey for 7.2% response rate. 44% had a COST score <26, indicating financial toxicity. Patients with high financial toxicity were more likely to be younger (mean age 54 vs 60), have cervical cancer (10% vs 4%; p=0.008), be privately insured (71% vs 57%; p=0.003) or have Medicaid (7% vs 3%; p=0.03), or be unemployed (18% vs 3%; p=<0.001), and less likely to be white (79% vs 90%, p=0.003) than those with low financial toxicity. Patients with Medicare were less likely to experience financial toxicity than privately insured patients (RR=0.59, 95% CI 0.37 to 0.95).

In this study of patients with gynecologic cancer or pre-cancer, 44% had financial toxicity. Financial toxicity was higher in patients who were younger, did not identify as White, and had private insurance. Targeted measures to address financial toxicity are needed to minimize disparities in patient burden of cancer treatment.

Hair ageing is accompanied by hair fibres becoming irregularly shaped causing them to stick out in irregular directions or have more curliness and being spread out. This is believed to be due to changes within the hair fibre structure which occur with ageing, and one of the causes of these changes could be an increase in the number of protein carbonyl groups present in the hair. The aim of this study is to investigate the internal denaturation of hair related to protein carbonyls in attempt to gain new insight into age-related changes that occur in hair.

The degree of carbonylation of the hair structural protein as determined by fluorescent labelling and Western blotting analysis was used to investigate the primary structure of hair protein. The amount of helix, a common conformation in the secondary structure of proteins, in hair in groups of women with different ages was also analysed using infrared microscopy coupled with multivariate curve resolution (MCR). From the results of this, an image of the two-dimensional distribution of the α-helices was generated for the hair taken from each age group. Also, high-pressure differential scanning calorimetry (HPDSC) of the hair in water was performed on the hair taken from each age group to determine the peak temperature of endothermic effect and the enthalpy of denaturation.

We found that the amino group content in hair proteins decreased and Type II keratin, one of the subunits of intermediate filament, was more carbonylated with age. The results of the MCR indicated eight separate components, including components of the secondary structure of proteins, such as α helices and β sheets. Two-dimensional images of the hair cross-sections revealed that the presence of α helices decreased with age. In addition, data from the HPDSC showed that the enthalpy associated with the denaturing temperature also significantly decreased with age.

These results suggest that there is a negative correlation between age and structural integrity of the helix segment in intermediate filament. The results of this study also show that there is a positive correlation between age-related hair denaturation and protein carbonyls.

Computed tomography (CT) is routinely used to guide cryoablation procedures. Notably, CT-guidance provides 3D localization of cryoprobes and can be used to delineate frozen tissue during ablation. However, metal-induced artifacts from ablation probes can make accurate probe placement challenging and degrade the ice ball conspicuity, which in combination could lead to undertreatment of potentially curable lesions.

In this work, we propose an image-based neural network (CNN) model for metal artifact reduction for CT-guided interventional procedures.

An image domain metal artifact simulation framework was developed and validated for deep-learning-based metal artifact reduction for interventional oncology (MARIO). CT scans were acquired for 19 different cryoablation probe configurations. The probe configurations varied in the number of probes and the relative orientations. A combination of intensity thresholding and masking based on maximum intensity projections (MIPs) was used to segment both the probes only and probes + artifact in each phantom image. Each of the probe and probe + artifact images were then inserted into 19 unique patient exams, in the image domain, to simulate metal artifact appearance for CT-guided interventional oncology procedures. The resulting 361 pairs of simulated image volumes were partitioned into disjoint training and test datasets of 304 and 57 volumes, respectively. From the training partition, 116 600 image patches with a shape of 128 × 128 × 5 pixels were randomly extracted to be used for training data. The input images consisted of a superposition of the patient and probe + artifact images. The target images consisted of a superposition of the patient and probe only images. This dataset was used to optimize a U-Net type model. The trained model was then applied to 50 independent, previously unseen CT images obtained during renal cryoablations. Three board-certified radiologists with experience in CT-guided ablations performed a blinded review of the MARIO images. A total of 100 images (50 original, 50 MARIO processed) were assessed across different aspects of image quality on a 4-point likert-type item. Statistical analyses were performed using Wilcoxon signed-rank test for paired samples.

Reader scores were significantly higher for MARIO processed images compared to the original images across all metrics (all p < 0.001). The average scores of the overall image quality, iceball conspicuity, overall metal artifact, needle tip visualization, target region confidence, and worst metal artifact, needle tip visualization, iceball conspicuity, and target region confidence improved by 34.91%, 36.29%, 39.94%, 34.17%, 35.13%, and 45.70%, respectively.

The proposed method of image-based metal artifact simulation can be used to train a MARIO algorithm to effectively reduce probe-related metal artifacts in CT-guided cryoablation procedures.

Biologics approved for psoriasis exhibit favorable safety profiles, and serious adverse events have rarely been reported. In this report, we present the case of a patient treated with ixekizumab, an anti-interleukin (IL)-17 agent, who 8 months later developed multiple sclerosis (MS). We also review the available literature regarding the use of anti-IL-17 agents in the context of psoriasis and pre-existing or new-onset demyelination. Eight case reports were evaluated as relevant and are presented in our report. In most of the cases secukinumab or ixekizumab administration adequately controlled both skin and pre-existing neurological clinical manifestations. However, there has been a report of MS exacerbation under secukinumab treatment and the occurrence of myelitis in a patient receiving ixekizumab. While the anti-IL-17-biologic-mediated induction of inflammatory events in the central nervous system has not been proven and a causal relationship is lacking, such a probability should be considered in extremely rare cases.

Neurocardiogenic injury is common after aneurysmal subarachnoid hemorrhage (aSAH) despite low prevalence of preexisting cardiac disease. Potential mechanisms include autonomic dysregulation due to excess catecholamines as well as systemic inflammation. Understanding how inflammation contributes to cardiac dysfunction may aid in identifying novel therapeutic strategies. Here, we investigated serum leukocytes as predictors of left ventricular systolic dysfunction in patients with aSAH. We also investigated increased cardiac macrophages in an animal model of SAH and whether immunomodulatory treatment could attenuate this inflammatory response.

We retrospectively analyzed 256 patients with aSAH admitted to University of Illinois Hospital between 2013 and 2019. Our inclusion criteria included patients with aSAH receiving an echocardiogram within 72 h of admission. Our primary outcome was echocardiographic evidence of systolic dysfunction. We performed multinomial regression and receiver operating curve analysis. We also used the endovascular perforation model of SAH in male Sprague-Dawley rats to assess for myocardial inflammation. Two days after surgery, hearts were collected and stained for the macrophage marker Iba-1. We compared the presence and morphology of macrophages in cardiac tissue isolated from SAH animals and sham controls treated with and without the immunomodulatory agent fingolimod.

Of 256 patients with aSAH, 233 (91.0%) underwent echocardiography within 72 h of admission. Of 233, 81 (34.7%) had systolic dysfunction. Patients had baseline differences in the presence of hypertension, alcohol use, and admission Glasgow Coma Scale and Hunt-Hess score. On multivariable analysis, total leukocytes (odds ratio 1.312, p < 0.001), neutrophils (odds ratio 1.242, p = 0.012), and monocytes (odds ratio 6.112, p = 0.008) were independent predictors of reduced systolic function, whereas only monocytes (odds ratio 28.014, p = 0.030) predicted hyperdynamic function. Within the rodent heart, there were increased macrophages after SAH relative to controls, and this was attenuated by fingolimod treatment (p < 0.0001).

Increased serum leukocytes are associated with abnormal left ventricular systolic function following aSAH. The strongest independent predictor of both reduced and hyperdynamic systolic function was increased monocytes. Increased cardiac macrophages after experimental SAH can also be targeted by using immunomodulatory drugs.

Phantoms are commonly used to evaluate and compare the performance of imaging systems given the known ground truth. Positron emission tomography (PET) scanners are routinely validated using the NEMA image quality phantom, in which lesions are modeled using 10 to 37 mm fillable spheres. The NEMA phantom neglects, however, to model focal (3-10-mm), high-uptake lesions that are increasingly observed in prostate-specific membrane antigen (PSMA) PET images. PSMA-targeting radiopharmaceuticals allow for enhanced detection of metastatic prostate cancers. As such, there is significant need to develop an updated phantom which considers both the quantitative and lesion detectability of this new paradigm in oncological PET imaging.

In this work, we present the Quantitative PET Prostate Phantom (Q3P); a portable and modular phantom that can be used to improve and harmonize imaging protocols for 18F-PSMA PET scans.

A one-piece cylindrical phantom was designed effectively in two halves, which we call modules. Module 1 was designed to mimic lesions in the presence of background, and Module 2 mimicked very high contrast conditions (i.e., very low background) that can be observed in 18F-PSMA PET scans. Shell-less radioactive spheres (3-16-mm) were cast using epoxy resin mixed with sodium-22 (22Na), a long half-life positron emitter with positron range similar to 18F. To establish realistic lesion contrast, the 22Na spheres were mounted in a cylindrical chamber that can be filled with an 18F background (module 1). Thirteen exchangeable spherical cavity inserts (3-37-mm) were machined in two parts and solvent welded together, and filled with 18F (50 kBq/mL) to model lesions with very high contrast (module 2). Five 2.5-min PET scans were acquired on a 5-ring GE Discovery MI PET/CT scanner (General Electric, USA). Lesions were segmented using 41% of SUVmax fixed thresholding (41% FT) and recovery coefficients (RCs) were computed from 5 noise realizations.

The manufactured phantom is portable (5.7 kg) and scan preparation takes less than 40 min. The total 22Na activity is 250 kBq, allowing it to be shipped as an exempt package under International Atomic Energy Agency (IAEA) regulations. Recovery coefficients, computed using PSF modeling and no post-reconstruction smoothing, were 130.3% (16 mm), 147.1% (10 mm), 87.2% (6 mm), and 7.0% (3 mm) for RCmax, which decreased to 91.1% (16 mm), 90.6% (10 mm), 53.2% (6 mm), and 3.6% (3 mm) for RCmean in the 22Na spheres. Comparatively, 18F sphere recovery was 110.7% (17 mm), 123.6% (10 mm), 106.5% (7 mm), and 23.3% (3 mm) for RCmax, which was reduced to 76.7% (17 mm), 77.7% (10 mm), 66.8% (7 mm), and 13.5% (3 mm), for RCmean.

A standardized imaging phantom was developed for lesion quantification assessment in 18F-PSMA PET images. The phantom is configurable, providing users with the opportunity to modify background activity levels or sphere sizes according to clinical demands. Distributed to the community, the Q3P phantom has the potential to enable better assessment of lesion quantification and harmonization of 18F-PSMA PET imaging, which may lead to more robust predictive metrics and better outcome prediction in metastatic prostate cancer.

The aim of this study was to compare the therapeutic effects of non-navigated freehand minimally invasive aspiration and conservative medical care in patients with deep supratentorial intracerebral hemorrhage (ICH).

We analyzed data from a prospective multicenter cohort study. Propensity score matching was performed to adjust for possible confounding factors. A total of 122 patients with first-onset deep supratentorial ICH with a volume ≥ 20 ml were enrolled. All patients were followed up at 30 days, 90 days, and 1 year. The mortality rate, functional outcomes, complications, and treatment costs were compared between the two groups.

After propensity score matching, 122 patients with a mean age of 56.0 years were included, 77.9% of whom were male. The median ICH volumes were 45.5 ml in the surgery group and 48.0 ml in the conservative group. The mortality rate at 30 days was significantly lower in the surgery group than in the conservative group (P = 0.0127). There were no significant differences in functional outcomes at the 90-day and 1-year follow-ups between the two groups (P > 0.05). There was no significant difference in complications, including recurrent bleeding (6.6% vs. 4.9%), pulmonary infection (57.4% vs. 41.0%), deep venous thrombosis (9.8% vs. 11.5%), heart failure (1.6% vs. 6.6%), and cerebral infarction (4.9% vs. 3.3%), between the two groups.

For deep supratentorial ICH, non-navigated freehand minimally invasive aspiration was safe and reduced short-term mortality but did not effectively improve long-term functional outcomes.

Patients with aneurysmal subarachnoid hemorrhage (aSAH) who survive the rupture are at risk for delayed neurologic deficits and cerebral infarction. The ideal method(s) of surveillance for cerebral vasospasm, and the link between radiographic vasospasm and delayed neurologic deficits, remain controversial. We instituted a postbleed day 7 angiography protocol with the stated goals of identification of vasospasm, improving neurologic outcomes, and possibly lowering cost of care.

We conducted a quality improvement project in which we retrospectively analyzed consecutive cases of aSAH from a single institution over a 5-year period. Patients were excluded if they did not receive treatment for their aneurysm or were < 18 years of age. We analyzed demographic and outcome information for patients managed by protocolled angiography versus those who were managed by as-needed endovascular rescue therapy. Statistical tests were performed comparing means and proportions in both cohorts, as appropriate.

In total, 223 patients were identified who met inclusion criteria. In total, 157 patients were identified in the protocolled day 7 angiography group, and 66 were in the nonprotocolled angiography group. Demographics were similar between the day 7 angiogram and medical management cohorts, except for a higher mean age among the latter group (p = 0.016). The protocolled angiography group underwent a significantly greater number of angiograms (p < 0.001) and had a significantly higher cost of hospitalization ($240,327 vs. $205,719, p = 0.03), with no significant difference in rate of cerebral infarction, length of intensive care unit stay, length of hospital stay, discharge location, or discharge modified Rankin Score.

This cohort comparison analysis draws into question the practice of protocolized cerebral angiography in patients with aSAH.

Disruption of the protective stratum corneum barrier increases the skin's vulnerability to microorganisms and facilitates conditions such as dandruff. Dandruff is a disorder of the scalp that causes increased scaling of the SC and is associated with Malassezia fungus. Consequently, many anti-dandruff commercial products use anti-fungal active ingredients such as piroctone olamine also known as Octopirox (OPX). OPX is an active ingredient used in a number of topical preparations for the management of dandruff. The characterization of the physicochemical properties of OPX was previously reported. The aim of the present work was to investigate a range of solvent systems for their effects on OPX interaction with human skin.

The solvents used in this study were propylene glycol (PG), diethylene glycol monoethyl ether or Transcutol® (TC), PG monolaurate (PGML), isopropyl myristate (IPM), caprylic/capric triglyceride or Labrafac™ Lipophile WL 1349 (LAB), PG caprylate or Capryol® 90 (CAP), isostearyl isostearate (ISIS) and Plurol® Oleique CC 497 (PIOI). The single solvent systems evaluated were PG, TC, PGML, IPM, ISIS and CAP. For the binary solvent systems, PG and TC were examined. Ternary solvent systems consisted of: PG, TC and LAB; PG, PGML and LAB; and PG, TC and IPM. The concentration of OPX used was 1% (w/v). Heat-separated human epidermis was used for 24 h permeation experiments performed under finite dose conditions; mass balance studies were also conducted.

For the six single solvents examined no permeation was evident. Skin permeation of OPX was observed for binary and ternary solvent systems. The highest permeation for all PG:TC binary solvent system ratios tested was from the PG:TC (75:25) system. For the ternary solvent systems investigated, highest cumulative permeation of OPX was observed for PG:PGML:LAB (60:30:10). Considering all systems, PG:TC (75:25) delivered the greatest amount of OPX through the skin. Although OPX is deposited in the skin following the application of neat solvents, higher skin retention values were generally observed for binary and ternary systems.

To our knowledge, this is the first study to examine the permeation behaviour of OPX for a range of single, binary and ternary solvent systems.

Mucormycoses are emerging fungal infections caused by a variety of heterogeneous species within the Mucorales order. Among the Mucor species complex, Mucor circinelloides is the most frequently isolated pathogen in mucormycosis patients and despite its clinical significance, there is an absence of established genome manipulation techniques to conduct molecular pathogenesis studies. In this study, we generated a spontaneous uracil auxotrophic strain and developed a genetic transformation procedure to analyze molecular mechanisms conferring antifungal drug resistance. With this new model, phenotypic analyses of gene deletion mutants were conducted to define Erg3 and Erg6a as key biosynthetic enzymes in the M. circinelloides ergosterol pathway. Erg3 is a C-5 sterol desaturase involved in growth, sporulation, virulence, and azole susceptibility. In other fungal pathogens, erg3 mutations confer azole resistance because Erg3 catalyzes the production of a toxic diol upon azole exposure. Surprisingly, M. circinelloides produces only trace amounts of this toxic diol and yet, it is still susceptible to posaconazole and isavuconazole due to alterations in membrane sterol composition. These alterations are severely aggravated by erg3Δ mutations, resulting in ergosterol depletion and consequently, hypersusceptibility to azoles. We also identified Erg6a as the main C-24 sterol methyltransferase, whose activity may be partially rescued by the paralogs Erg6b and Erg6c. Loss of Erg6a function diverts ergosterol synthesis to the production of cholesta-type sterols, resulting in resistance to amphotericin B. Our findings suggest that mutations or epimutations causing loss of Erg6 function may arise during human infections, resulting in antifungal drug resistance to first-line treatments against mucormycosis.

Systematic review.

To compare the efficacy of the posterior approach and combined anterior-posterior approach in the treatment of ankylosing spondylitis (AS) with cervical spine fracture by meta-analysis.

The databases PubMed, Web of Science, Embase, and Cochrane Library were searched for studies on the comparison of the posterior approach group and the combined anterior-posterior approach group in the treatment of ankylosing spondylitis combined with cervical spine fracture from database establishment to August 2023. The procedure time, intraoperative blood loss, the rates of neurological improvement, mean change in the postoperative neurological function, complication rates, rates of revised surgery, and mortality were extracted. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library.

A total of 11 retrospective cohort studies with a total of 215 patients were included in this study. The posterior approach group had lower intraoperative blood loss than the combined anterior-posterior approach group [Mean difference (MD) = -146.05, 95%CI(-187.40,-104.69), P < .00001]; the operation time was significantly less in the posterior approach group than in the combined anterior-posterior approach group [MD = -95.34, 95%CI(-113.13,-77.55), P < .00001]. There were no statistically significant differences in the neurological improvement rates, mean changes in postoperative neurological function, complication rates, modified surgery rates, and mortality rates.

Both the posterior approach and combined anterior and posterior approach can achieve good results. Clinicians should develop an individualized approach based on the patient's fracture type, degree of spinal cord injury, fracture stability, fracture dislocation, general condition, and underlying disease.

To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer.

Status epilepticus (SE) is a critical neurological emergency in patients with neurological and nonneurological diseases. Mortality rises with SE severity. However, whether brain injury or systemic organ dysfunction causes death after SE remains unclear. We studied clinical outcomes and systemic dysfunctions associated with SE using standardized data from the common data model. This model includes clinical evaluations and treatments that provide real-world evidence for standard practice.

This retrospective cohort study used the common data model database of a single tertiary academic medical center. Patients diagnosed with SE (corresponding to G41 of the International Classification of Diseases 10 and administration of antiseizure medication) between January 1, 2001, and January 1, 2018, were enrolled. Demographics, classifications of SE severity, and outcomes were collected as operational definitions by using a common data model format. Systemic complications were defined based on the Sequential Organ Failure Assessment criteria.

The electronic medical records of 1,825,196 patients were transformed into a common data model, and 410 patients were enrolled. The proportion of patients classified as having nonrefractory SE was 65.4% (268/410), followed by refractory (28.5%, 117/410) and super-refractory SE (6.1%, 25/410). Patients with more severe SE had longer intensive care unit and hospital stays. Renal dysfunction and thrombocytopenia were higher in the in-hospital death group (P = 0.002 and 0.003, respectively). In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II score and platelet count were significantly different in the in-hospital death group (odds ratio, 1.169, P = 0.004; and 0.989, P = 0.043).

Systemic complications after SE, especially low platelet counts, were linked to worse outcomes and increased mortality in a common data model. The common data model offers expandability and comprehensive analysis, making it a potentially valuable tool for SE research.

To evaluate the effectiveness of early initiation of angiotensin-converting enzyme inhibitor (ACEi) in patients with scleroderma renal crisis (SRC).

This was a retrospective cohort study using a nationwide inpatient database in Japan from July 2010 to March 2020. All hospitalized patients with SRC were divided into those who received ACEi within 2 days of admission (early ACEi group) and those who did not (control group). Propensity-score overlap weighting analysis was performed to adjust for confounding factors. The primary outcome was the composite of in-hospital mortality or haemodialysis dependence at discharge.

Of the 475 eligible patients, 248 (52.2%) were in the early ACEi group and 227 (47.8%) were in the control group. After overlap weighting, the primary outcome was significantly lower in the early ACEi group than in the control group (40.1% vs 49.0%; odds ratio, 0.69; 95% CI: 0.48, 1.00; P = 0.049).

The present study showed that early initiation of ACEi was associated with lower composite outcome of in-hospital mortality or haemodialysis dependence at discharge in patients with SRC. Further prospective studies are warranted to verify the present findings.