Characterization of Chronic Graft-versus-host Disease After Haploidentical Stem Cell Transplantation With Posttransplant Cyclophosphamide: A Study on Behalf of GETH-TC.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is a cause of late morbidity and nonrelapse mortality (NRM) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Although studies evaluating haploidentical allo-HSCT (haplo-HSCT) using posttransplant cyclophosphamide (PTCy) demonstrate lower cGVHD rates, comprehensive data describing the clinical profile, risk factors, or outcomes of cGVHD within this platform are scarce. METHODS: We conducted a retrospective multicenter analysis of 389 consecutive patients who underwent haplo-HSCT PTCy in 7 transplant centers of the Spanish Group Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) between 2008 and 2020 describing incidence, clinical profile, risk factors, and cGVHD outcomes. RESULTS: Ninety-five patients of 389 developed cGVHD. Our data revealed that the incidence and severity of cGVHD are lower than those reported for HLA-identical transplantation with conventional prophylaxis and that the strongest predictor for cGVHD was previous acute GVHD (P = 0.031). Also, recipient age ≥60 y (P = 0.044) was protective against cGVHD. Moreover, patients with moderate cGVHD had longer event-free survival at 3 y than other patients (P = 0.016) and a lower relapse rate at 3 y (P = 0.036). CONCLUSIONS: Our results support the fact that the incidence and severity of cGVHD are lower than those reported for HLA-identical transplantation with conventional prophylaxis. In this series, patients who develop moderate cGVHD after haplo-HSCT PTCy had a higher overall survival and event-free survival, and lower relapse, suggesting higher graft-versus-leukemia effect. Although this is the largest series focused on characterizing cGVHD in haplo-HSCT PTCy, further prospective studies are needed to confirm the findings.

Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso / Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report. / Trasplante de médula ósea haploidéntico en un paciente pediátrico con síndrome de Wiskott-Aldrich. A propósito de un caso.

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.

Conversion of a dysfunctional choledochoduodenostomy to transpapillary drainage via a trans-lumen-apposing metal stent choledochoduodenoscopy.

Video 1Peroral antegrade cholangioscopy-guided conversion of dysfunctional choledochoduodenostomy to transpapillary drainage via trans-LAMS (lumen-apposing metal stent).

Domain-specific neuropsychological investigation of CAA with and without intracerebral haemorrhage.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with cognitive impairment, but the contributions of lobar intracerebral haemorrhage (ICH), underlying diffuse vasculopathy, and neurodegeneration, remain uncertain. We investigated the domain-specific neuropsychological profile of CAA with and without ICH, and their associations with structural neuroimaging features. METHODS: Data were collected from patients with possible or probable CAA attending a specialist outpatient clinic. Patients completed standardised neuropsychological assessment covering seven domains. MRI scans were scored for markers of cerebral small vessel disease and neurodegeneration. Patients were grouped into those with and without a macro-haemorrhage (CAA-ICH and CAA-non-ICH). RESULTS: We included 77 participants (mean age 72, 65% male). 26/32 (81%) CAA-non-ICH patients and 41/45 (91%) CAA-ICH patients were impaired in at least one cognitive domain. Verbal IQ and non-verbal IQ were the most frequently impaired, followed by executive functions and processing speed. We found no significant differences in the frequency of impairment across domains between the two groups. Medial temporal atrophy was the imaging feature most consistently associated with cognitive impairment (both overall and in individual domains) in both univariable and multivariable analyses. DISCUSSION: Cognitive impairment is common in CAA, even in the absence of ICH, suggesting a key role for diffuse processes related to small vessel disease and/or neurodegeneration. Our findings indicate that neurodegeneration, possibly due to co-existing Alzheimer's disease pathology, may be the most important contributor. The observation that general intelligence is the most frequently affected domain suggests that CAA has a generalised rather than focal cognitive impact.

Determination of several PFAS groups in food packaging material from fast-food restaurants in France.

Per- and polyfluoroalkylated substances (PFAS) are a large group of toxic compounds which have been widely used in industrial and consumer applications, from where they can migrate into the environment. They can pose a risk to human health because they have been associated with several diseases. To obtain more information on the risk of PFAS in fast food packaging materials, several PFAS (perfluorocarboxylic acids or PFCAs (n = 16), perfluorosulfonic acids or PFSAs (n = 14), and a miscellaneous group constituted by sulfonamides (n = 5) and fluorotelomer phosphate esters or PAPs (n = 5)) were quantified in food contact materials (FCMs) from fast-food restaurants in France. Perfluorohexanoic acid (PFHxA), 6:2 fluorotelomer sulfonic acid (6:2 FTS) and 6:2/6:2 fluorotelomer phosphate diester (6:2/6:2 diPAP) were detected in all samples. PFCAs with shorter chain lengths (C4-C6) showed the highest concentrations compared to median (C7-C10) and longer chain length PFCAs (C11-C18). However, they had lower detection frequencies (DFs) (except for PFHxA, DF = 100%) with values of 36 and 34% for C4 and C5 PFCAs, respectively. The DF of longer chain length PFCAs was higher, especially those of the median chain length PFCAs (C8-C10, with DF = 79-98%). Analytes from the PFSA group with high DFs (70-98%) were perfluorobutane sulfonic acid (PFBS), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS, linear and branched) and 10:2 fluorotelomer sulfonic acid (10:2 FTS), with concentrations similar to some analytes from the PFCA group. 4:2 Fluorotelomer phosphate monoester (4:2 mPAP), 8:2 fluorotelomer phosphate monoester (8:2 mPAP) and 8:2/8:2 fluorotelomer phosphate diester (8:2/8:2 diPAP) were found with the highest concentrations (<0.006-42.7 ng g-1, <0.001-2.7 ng g-1 and <0.001-287 ng g-1, respectively) and the highest DFs (ranged 68-94%). Some correlations between analytes were found, indicating similar degradation routes or a common origin.

Papel de las estatinas en la evolución clínica de los pacientes octogenarios ingresados por COVID-19 / Role of statins in clinical evolution of octogenarian patients admitted due to COVID-19

antecedentes y objetivos La coronavirus disease 2019 (COVID-19) produce una elevada mortalidad en pacientes ancianos. Algunos estudios han señalado un beneficio del tratamiento con estatinas en la evolución de esta enfermedad. El objetivo de este estudio es analizar la mortalidad intrahospitalaria en relación al tratamiento previo al ingreso con estatinas en una población de pacientes octogenarios, ya que no existen estudios específicamente en este grupo de población. Materiales y métodos Se realizó un estudio de cohortes retrospectivo unicéntrico incluyendo un total de 258 pacientes ≥80 años con ingreso hospitalario por COVID-19 confirmada, entre el 1 de marzo y el 31 de mayo de 2020. Se dividieron en dos grupos: toma de estatinas previas al ingreso (n = 129) o no (n=129). Resultados La mortalidad intrahospitalaria por COVID-19 en pacientes ≥ 80 años (86,13+-4,40) durante la primera ola fue del 35,7% (IC 95%:30 1-41,7%). La mortalidad de los pacientes que tomaban previamente estatinas fue del 25,6% mientras que la de aquellos que no las tomaban fue del 45,7%. El sexo femenino (RR 0,62 IC 95%[0,44-0,89]; p 0,008), la diabetes (RR 0,61 IC 95% [0,41-0,92];p 0,017) y el tratamiento previo al ingreso con estatinas (RR 0,58 IC 95% [0,41-0,83]; p 0,003) se asociaron a una menor mortalidad intrahospitalaria. La afectación pulmonar grave se asoció a un aumento de la mortalidad intrahospitalaria (RR 1,45 IC 95% [1,04-2,03]; p 0,028). La hipertensión arterial, la obesidad, la edad, la enfermedad cardiovascular y un mayor índice de Charlson no mostraron sin embargo influencia sobre la mortalidad intrahospitalaria. Conclusiones En pacientes octogenarios tratados con estatinas previo al ingreso por COVID-19 se observó una menor mortalidad intrahospitalaria en la primera ola (AU)

Introduction and objectives coronavirus disease 2019 (COVID-19) causes high mortality in elderly patients. Some studies have shown a benefit of statin treatment in the evolution of this disease. Since there are no similar publications in this population group, the aim of this study is to analyze in-hospital mortality in relation to preadmission treatment with statins in an exclusively elderly population of octogenarian patients. Materials and methods A single-center retrospective cohort study was performed including a total of 258 patients ≥80 years with hospital admission for confirmed COVID-19 between March 1 and May 31, 2020. They were divided into two groups: taking statins prior to admission (n=129) or not (n=129). Results In-hospital mortality due to COVID-19 in patients ≥80 years (86.13±4.40) during the first wave was 35.7% (95% CI: 30.1–41.7%). Mortality in patients previously taking statins was 25.6% while in those not taking statins was 45.7%. Female sex (RR 0.62 [0.44-0.89]; p=0.008), diabetes (RR 0.61 [0.41-0.92]; p=0.017) and pre-admission treatment with statins (RR 0.58 95% CI [0.41-0.83]; p=0.003) were associated with lower in-hospital mortality. Severe lung involvement was associated with increased in-hospital mortality (RR 1.45 95% CI [1.04-2.03]; p=0.028). Hypertension, obesity, age, cardiovascular disease and a higher Charlson index did not, however, show influence on in-hospital mortality. Conclusions In octogenarian patients treated with statins prior to admission for COVID-19 in the first wave, lower in-hospital mortality was observed (AU)

Nanoemulsion Increases the Antifungal Activity of Amphotericin B against Four Candida auris Clades: In Vitro and In Vivo Assays.

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.

Heat-Priming during Somatic Embryogenesis Increased Resilience to Drought Stress in the Generated Maritime Pine (Pinus pinaster) Plants.

Drought stress is becoming the most important factor of global warming in forests, hampering the production of reproductive material with improved resilience. Previously, we reported that heat-priming maritime pine (Pinus pinaster) megagametophytes during SE produced epigenetic changes that generated plants better adapted to subsequent heat stress. In this work, we tested, in an experiment performed under greenhouse conditions, whether heat-priming will produce cross-tolerance to mild drought stress (30 days) in 3-year-old priming-derived plants. We found that they maintain constitutive physiological differences as compared to controls, such as higher proline, abscisic acid, starch, and reduced glutathione and total protein contents, as well as higher ΦPSII yield. Primed plants also displayed a constitutive upregulation of the WRKY transcription factor and the Responsive to Dehydration 22 (RD22) genes, as well as of those coding for antioxidant enzymes (APX, SOD, and GST) and for proteins that avoid cell damage (HSP70 and DHNs). Furthermore, osmoprotectants as total soluble sugars and proteins were early accumulated in primed plants during the stress. Prolongated water withdrawal increased ABA accumulation and negatively affected photosynthesis in all plants but primed-derived plants recovered faster than controls. We concluded that high temperature pulses during somatic embryogenesis resulted in transcriptomic and physiological changes in maritime pine plants that can increase their resilience to drought stress, since heat-primed plants exhibit permanent activation of mechanisms for cell protection and overexpression of stress pathways that pre-adapt them to respond more efficiently to soil water deficit.

Human Papilloma Virus DNA Detection in Clinical Samples Using Fluorogenic Probes Based on Oligonucleotide Gated Nanoporous Anodic Alumina Films.

In this work, fluorogenic probes based on oligonucleotide capped nanoporous anodic alumina films are developed for specific and sensitive detection of human papilloma virus (HPV) DNA. The probe consists of anodic alumina nanoporous films loaded with the fluorophore rhodamine B (RhB) and capped with oligonucleotides bearing specific base sequences complementary to genetic material of different high-risk (hr) HPV types. Synthesis protocol is optimized for scale up production of sensors with high reproducibility. The sensors' surfaces are characterized by scanning electron microscopy (HR-FESEM) and atomic force microscopy (AFM) and their atomic composition is determined by energy dispersive X-ray spectroscopy (EDXS). Oligonucleotide molecules onto nanoporous films block the pores and avoid diffusion of RhB to the liquid phase. Pore opening is produced when specific DNA of HPV is present in the medium, resulting in RhB delivery, that is detected by fluorescence measurements. The sensing assay is optimized for reliable fluorescence signal reading. Nine different sensors are synthesized for specific detection of 14 different hr-HPV types in clinical samples with very high sensitivity (100%) and high selectivity (93-100%), allowing rapid screening of virus infections with very high negative predictive values (100%).

[Role of statins in clinical evolution of octogenarian patients admitted due to COVID-19]. / Papel de las estatinas en la evolución clínica de los pacientes octogenarios ingresados por COVID-19.

INTRODUCTION AND OBJECTIVES: coronavirus disease 2019 (COVID-19) causes high mortality in elderly patients. Some studies have shown a benefit of statin treatment in the evolution of this disease. Since there are no similar publications in this population group, the aim of this study is to analyze in-hospital mortality in relation to preadmission treatment with statins in an exclusively elderly population of octogenarian patients. MATERIALS AND METHODS: A single-center retrospective cohort study was performed including a total of 258 patients ≥80 years with hospital admission for confirmed COVID-19 between March 1 and May 31, 2020. They were divided into two groups: taking statins prior to admission (n=129) or not (n=129). RESULTS: In-hospital mortality due to COVID-19 in patients ≥80 years (86.13±4.40) during the first wave was 35.7% (95% CI: 30.1-41.7%). Mortality in patients previously taking statins was 25.6% while in those not taking statins was 45.7%. Female sex (RR 0.62 [0.44-0.89]; p=0.008), diabetes (RR 0.61 [0.41-0.92]; p=0.017) and pre-admission treatment with statins (RR 0.58 95% CI [0.41-0.83]; p=0.003) were associated with lower in-hospital mortality. Severe lung involvement was associated with increased in-hospital mortality (RR 1.45 95% CI [1.04-2.03]; p=0.028). Hypertension, obesity, age, cardiovascular disease and a higher Charlson index did not, however, show influence on in-hospital mortality. CONCLUSIONS: In octogenarian patients treated with statins prior to admission for COVID-19 in the first wave, lower in-hospital mortality was observed.

Newspaper Coverage and Framing of Bats, and Their Impact on Readership Engagement.

The media is a valuable pathway for transforming people's attitudes towards conservation issues. Understanding how bats are framed in the media is hence essential for bat conservation, particularly considering the recent fearmongering and misinformation about the risks posed by bats. We reviewed bat-related articles published online no later than 2019 (before the recent COVID19 pandemic), in 15 newspapers from the five most populated countries in Western Europe. We examined the extent to which bats were presented as a threat to human health and the assumed general attitudes towards bats that such articles supported. We quantified press coverage on bat conservation values and evaluated whether the country and political stance had any information bias. Finally, we assessed their terminology and, for the first time, modelled the active response from the readership based on the number of online comments. Out of 1095 articles sampled, 17% focused on bats and diseases, 53% on a range of ecological and conservation topics, and 30% only mention bats anecdotally. While most of the ecological articles did not present bats as a threat (97%), most articles focusing on diseases did so (80%). Ecosystem services were mentioned on very few occasions in both types (< 30%), and references to the economic benefits they provide were meagre (< 4%). Disease-related concepts were recurrent, and those articles that framed bats as a threat were the ones that garnered the highest number of comments. Therefore, we encourage the media to play a more proactive role in reinforcing positive conservation messaging by presenting the myriad ways in which bats contribute to safeguarding human well-being and ecosystem functioning.

Supramolecular solvent extraction and ambient mass spectrometry for the determination of organic contaminants in food packaging material.

A rapid method based on a fast sample treatment with supramolecular solvents (SUPRASs) and ambient mass spectrometry (AMS) analysis was developed for the screening and quantification of organic contaminants in food packaging materials (FCMs). The suitability of SUPRASs made up of medium chain alcohols in ethanol:water mixtures was investigated, given their low toxicity, proven capacity for multi-residue analysis (since they provide a wide variety of interactions and multiple binding sites) and restricted access properties for simultaneous sample extraction and clean-up. Two families of emerging organic pollutants, bisphenols and organophosphate flame retardants, were targeted as representative compounds. The methodology was applied to 40 FCMs. Target compounds were quantitated using ASAP (atmospheric solids analysis probe)-low resolution MS and a broad-spectrum screening of contaminants was performed through spectral library search using direct injection probe (DIP) and high resolution MS (HRMS). The results showed the ubiquity of bisphenols and of some flame retardants, as well as the presence of other additives and unknown compounds in about half of the analyzed samples, which highlight the complex composition of FCMs and the possible associated health risks.

Climate change, animals, and Candida auris: insights into the ecological niche of a new species from a One Health approach.

BACKGROUND: One of the most puzzling traits of Candida auris is the recent simultaneous and independent emergence of five genetically distinct clades on three continents. Global warming has been proposed as a contributing factor for this emergence owing to high thermotolerance of C. auris compared with phylogenetically close Candida species. This hypothesis postulates that climate change induced an environmental ancestor to become pathogenic through thermal adaptation and was then globally disseminated by an intermediate host. OBJECTIVES: The aim of this review is to compile the current knowledge on the emergence and ecological environmental niches of C. auris and highlight the potential role of animals in transmission. SOURCES: A literature search was conducted using PubMed, MEDLINE, Google Scholar, and Web of Science from May 2022 to January 2023. CONTENT: We discuss the up-to-date data on the ecological niches of this fungus and its mechanisms of emergence, transmission cycle in nature, and worldwide dissemination. We highlight the possibility of an originally intermediate host possibly related to marine or freshwater ecosystems on the basis of recent molecular and microbiological evidence from a One Health perspective. The consequences of harmful human impact on the environment in the rise of new fungal pathogenic species, such as C. auris, are also analysed and compared with other animal precedents. IMPLICATIONS: The present knowledge can prompt the generation of new evidence on the ecological reservoirs of C. auris and its original mechanisms of environmental or interspecies transmission. Further research on the highlighted gaps will help understand the importance of the relationships between human, animal, and ecosystem health as factors involved in the rise and spread of emerging fungal pathogenic species.