bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Implementation of Art. 17 DSM Directive in Germany – A Primer with Some Comparative Remarks
Authors: Leistner Matthias 
Published: September 2022

Abstract
The CJEU’s judgment in Case 401/19 (Poland v EU Parliament and Council) of April 2022 has unambiguously settled that, if it is to be in line with EU constitutional law, Art. 17 DSM Directive has to be implemented and applied in a balanced way to prevent the immediate ex ante blocking of contents which do not manifestly infringe copyright. Germany (and Austria) have implemented Art. 17 in their national laws in such a balanced way that provides for a delayed takedown for contents which can be presumed to be covered by exceptions to copyright law. This paper outlines the structure and workability of the German implementation law which now, after the CJEU judgment, in fact is a genuine (and perhaps the only reasonable) model for implementation in other Member States which have not yet implemented Art. 17.
Specific Associations Between Type of Childhood Abuse and Elevated C-Reactive Protein in Young Adult Psychiatric Rehabilitation Participants
Authors: Jabbi Mbemba M , Harvey Philip D , Kotwicki Raymond J , Nemeroff Charles B 
Published: September 2022

Abstract

Background
Early-life adversity such as childhood emotional, physical, and sexual trauma is associated with later-life psychiatric and chronic medical conditions, including elevated inflammatory markers. Although previous research suggests a role for chronic inflammatory dysfunctions in several disease etiologies, specific associations between childhood trauma types and later-life inflammation and health status are poorly understood.

Methods
We studied patients (n = 280) admitted to a psychiatric rehabilitation center. Self-reported histories of childhood emotional, physical, and sexual trauma were collected with a standard instrument. At the time of admission, we also assessed individuals’ body mass index and collected blood samples used to examine inflammatory marker C-reactive protein (CRP) levels.

Results
The prevalence of all 3 types of abuse was relatively high at 21% or more. Fifty percent of the sample had elevations in CRP, with clinically significant elevations in 26%. We found that compared with a history of emotional or physical abuse, a history of childhood sexual trauma was more specifically associated with elevated CRP. This result held up when using linear regressions to examine the contribution of body mass index.

Limitation
Our sample was relatively young, with an average age of 27.2 years and minimal representation of ethnic and racial minority participants.

Conclusion
Relative to childhood emotional and physical trauma, childhood sexual trauma may lead to elevated inflammatory responses, as confirmed in our finding of an association between CRP and sexual abuse. Future studies need to assess the causal link between childhood sexual trauma and poorer health outcomes later in life.
A fundamental change emerging in locally advanced rectal cancer management: a case report
Authors: Edwards-Murphy Amy , Earley Helen , Creavin Ben , McCullough Peter , Cooke Fiachra , Neary Peter 
Published: September 2022

Abstract
Treatment of locally advanced rectal cancer remains a challenge in colorectal surgery. It has had an evolving landscape over the past three decades. Implementation of total neoadjuvant therapy (TNT) as a novel approach to management has begun globally but long-term outcomes and data analysis to identify optimal schedules are eagerly awaited. We report a case of locally advanced rectal cancer management in a young male with a complete pathological response to TNT.
A rare case of azygous vein aneurysm with cotriatrium dextrum
Authors: Chandrakumanan Ashviini , Tee Sui Wu , Sylverster Melvin , Richards Avisha , Chew Loon Guan 
Published: September 2022

Abstract
Azygous vein aneurysm (AVA) is an infrequent entity for posterior mediastinal lesion and paratracheal mass. Usually asymptomatic, AVA is discovered during routine examination of a patient. The patho-etiology of the azygous vein aneurysm has not been fully understood till date, making it difficult to postulate the most common cause for its occurrence. Nonetheless, AVA has to be taken into consideration as a differential diagnosis for posterior mediastinal mass or right paratracheal lesion. The objective of this paper is to report a rare case of AVA and further discuss on its patho-etiology leading to the dilatation of azygous vein aneurysm.
Multiple plasma membrane SLC4s contribute to external HCO3– acquisition during CO2 starvation in the marine diatom Phaeodactylum tricornutum
Authors: Nawaly Hermanus , Matsui Hiroaki , Tsuji Yoshinori , Iwayama Kazufumi , Ohashi Hiroki , Nakajima Kensuke , Matsuda Yusuke 
Published: September 2022

Abstract
The availability of CO2 is one of the restrictions on aquatic photosynthesis. Solute carrier (SLC) 4-2, a plasma membrane HCO3– transporter has previously been identified in the marine diatom Phaeodactylum tricornutum. In this study, we discovered two paralogs, PtSLC4-1 and PtSLC4-4, that are both localized at the plasma membrane. Their overexpression stimulated HCO3– uptake, and this was inhibited by the anion channel blocker 4,4´-diisothiocyanostilbene-2,2´-disulfonic (DIDS). Similarly to SLC4-2, PtSLC4-1 specifically required Na+ of ~100 mM for its maximum HCO3– transport activity. Unlike PtSLC4-1 and PtSLC4-2, the HCO3– transport of PtSLC4-4 depended equally on Na+, K+, or Li+, suggesting its broad selectivity for cations. Transcript analyses indicated that PtSLC4-1 was the most abundant HCO3– transporter under CO2 concentrations below atmospheric levels, while PtSLC4-4 showed little transcript induction under atmospheric CO2 but transient induction to comparable levels to PtSLC4-1 during the initial acclimation stage from high CO2 (1%) to very low CO2 (&lt;0.002%). Our results strongly suggest a major HCO3– transport role of PtSLC4-1 with a relatively minor role of PtSLC4-2, and that PtSLC4-4 operates under severe CO2 limitation unselectively to cations when the other SLC4s do not function to support HCO3– uptake.
AtHD2D, a plant-specific histone deacetylase involved in abscisic acid response and lateral root development
Authors: Zhang Zhaochen , Yang Weixia , Chu Yueyang , Yin Xiaotong , Liang Yueqi , Wang Qiuping , Wang Lei , Han Zhaofen 
Published: September 2022

AbstractIn eukaryotes, histone acetylation levels directly regulate downstream gene expression. As a plant-specific histone deacetylase (HDAC), HD2D is involved in plant development and abiotic stress. However, the response of HD2D to drought stress and its interacting proteins, is still unclear. In this study, we analysed HD2D gene expression patterns in Arabidopsis, revealing that HD2D gene was highly expressed in roots and rosette leaves, but poorly expressed in other tissues such as stems, flowers, and young siliques. The HD2D gene expression was induced by d-mannitol. We investigated the responses to drought stress in the wild-type plant, HD2D overexpression lines, and hd2d mutants. HD2D-overexpressing lines showed abscisic acid (ABA) hypersensitivity and drought tolerance, and these phenotypes were not present in hd2d mutants. RNA-seq analysis revealed the transcriptome changes caused by HD2D under drought stress, and showed that HD2D responded to drought stress via the ABA signalling pathway. In addition, we demonstrated that CASEIN KINASE II (CKA4) directly interacted with HD2D. The phosphorylation of Ser residues on HD2D by CKA4 enhanced HD2D enzymatic activity. Furthermore, the phosphorylation of HD2D was shown to contribute to lateral root development and ABA sensing in Arabidopsis, but, these phenotypes could not be reproduced by the overexpression of Ser-phospho-null HD2D lines. Collectively, this study suggests that HD2D responded to drought stress by regulating the ABA signalling pathway, and the expression of drought stress-related genes. The regulatory mechanism of HD2D mediated by CKII phosphorylation provides new insights into the ABA response and lateral root development in Arabidopsis.
P002 Antifungal activity of antimicrobial synthetic peptides against Candida species of public health importance
Authors: Torres Richar , Barreto-Santamaría Adriana , Arévalo-Pinzón PhD Gabriela , Escandón Patricia , Firacative Carolina , Gómez Beatriz L , Patarroyo Manuel A , Muñoz Phd Julian E 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Background
Candidiasis is one of the most frequent opportunistic infections in immunosuppressed and/or hospitalized patients. In countries like Colombia, candidiasis is associated with a mortality rate of ∼ 46%. Growing pharmacological resistance of Candida spp., and the appearance of the emerging pathogen Candida auris, have turned candidiasis into a major public health problem. Different types of antimicrobial peptides have been investigated as a therapeutic alternative to control candidiasis effectively and safely.

Objective
This work aimed at evaluating the in vitro antifungal activity of three synthetic antimicrobial peptides (35 409, 1609, and 29 009) obtained from Plasmodium falciparum Rif1 protein against C. auris, C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis, species with worldwide clinical importance.

Methods
The minimum inhibitory concentrations (MIC) of the three peptides against Candida species were determined by the plate microdilution method; the peptides’ effect on biofilm formation in C. auris and C. albicans species was also evaluated through the XTT metabolic activity assay. Additionally, the structural damages in C. auris and C. albicans caused by the action of the peptides were observed by transmission electron microscopy (TEM) and finally, the in vitro peptides’ cytotoxicity against L929 murine fibroblasts was verified.

Results
Our findings showed that the three peptides herein evaluated, displayed antifungal activity in both planktonic and sessile Candida cells. Likewise, the TEM evidenced morphological alterations induced by the peptides, both in the membrane and at the intracellular level of the yeasts. As well, total safety against the murine cell line L929 with 24 h of treatment was observed.

Conclusions
From these results, we conclude that the antimicrobial peptides 35 409, 1609, and 29 009 are potential therapeutic alternatives against the most important Candida species in Colombia and the world.
P011 Antifungal lock therapy
Authors: Koparkar Vidyullata , Soman Rajeev , Shetty Anjali , Purandare Bharat , Sunavala Ayesha , Doshi Aakash 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objective
Candida spp is the fourth leading cause of catheter-related blood stream infection (CRBSI). The standard treatment is prompt removal of the device (central venous catheter, CVC, or port or hemodialysis catheter) along with administration of systemic antifungal therapy. However, in patients with a lack of alternative intravenous access and in some critically ill patients, this standard of care is challenging. Our success with antibiotic lock solution in MDR GNB CRBSI, prompted us to consider similar therapy in Candida spp CRBSI.

Methods
Catheter salvage using antifungal lock therapy was tried in a total of 15 cases in two centers. In 10 cases echinocandin (9 anidulafungin, 1 micafungin) and in 5 cases amphotericin b deoxycholate (AmB-d) were used to obtain an antifungal concentration of ∼ 1000 mcg/ml in the lock solutions. All these formulations had additional NAC, heparin, and normal saline. Systemic antifungal therapy was also administered concurrently.
Success was defined as clearance of candidemia at 48 h and 14 days and/or till the use of the device was needed. Some of these patients had prior/co-infections with bacterial pathogens and they were managed with appropriate systemic antibiotics with antibiotic lock therapy.

Results
In 11/15 episodes of CRBSI due to Candida species, catheter salvage was achieved. One case could not be assessed at 14 days as a port was removed in view of megaprosthesis in situ. In two cases this therapy failed and one patient lost to follow-up.
See Figures 1 and 2 for details of all cases.

Conclusions
Antifungal lock therapy using echinocandins and AmB-d appears to be a promising therapy in patients where catheter removal is difficult. However, this success neither means that this can become standard practice, nor should it make clinicians and hospital staff complacent about infection control practices.
P025 A study on candiduria in neonates and infants from a tertiary care center, North India.
Authors: Yadav Renu , Xess Immaculata , Singh Gagandeep , Rana Bhaskar , CS Saumya 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objective
Candida albicans is the major cause of fungal UTI in neonates and infants but nowadays incidence of other species of Candida is also increasing, and these are mostly multidrug resistant. It is, therefore, important to determine the causative Candida species in fungal UTI for appropriate management. This study was undertaken to determine the Candida species distribution in UTI along with susceptibility patterns and outcomes in infants and neonates admitted to various wards and intensive care units (ICUs) of our hospital. The incidence rate of candiduria in ICUs was also assessed.

Method
Urine samples were collected from infants and neonates presented in pediatric and neonatal ICUs and clinical wards with a clinical suspicion of candiduria. Infants at risk of invasive candidiasis were also included in the study. Identification of Candida species was done by Gram's staining, germ tube test, chlamydospore formation on corn meal agar, color of colonies on CHROMagar, and confirmed by Matrix Assisted Laser Desorption-Time of Flight (MALDI-TOF). Antifungal susceptibility was performed by using the Broth microdilution method as per the latest CLSI guidelines (M27-A3/M27-S4).

Result
Urine samples were received from 219 infants, and Candida was isolated from samples from 52 infants (isolation rate 23.75%), of which 30 were admitted to pediatric or neonatal ICU and 22 in the wards. The incidence rate of candiduria in ICU was 3.25%. Candida albicans was the most frequently isolated species from the samples of infants in the wards (13/22 ie, 59%), while Candida tropicalis was most frequently isolated from samples of infants in the ICUs (13/30 ie, 43.34%). Candida glabrata was the least commonly isolated species and was only encountered in the ICU. The species distribution of isolates is given in Table 1. There was no discrepancy between the results of conventional methods of identification and MALDI-TOF.
Antifungal susceptibility was performed for 18 randomly selected isolates. All were found to be susceptible to caspofungin, micafungin, itraconazole, voriconazole, fluconazole, and amphotericin B. MIC distribution for various isolates is given in Table 2.

Conclusion
High index of suspicion of candiduria is necessary for early diagnosis of fungal UTI and initiation of antifungal treatment, especially in critically ill infants requiring intensive care. Species other than C. albicans are also encountered more frequently nowadays and these species often have higher MICs for commonly used antifungal drugs, which may lead to delayed or failed response to routine antifungal therapy and necessitate prolonged use and or higher doses of antifungals. Identification of Candida isolates at species level along with analysis of the susceptibility patterns is therefore important for successful outcomes in candiduria in neonates and infants.
P026 Antifungal activity of a novel triazole and comparators against a large collection of identified Aspergillus isolates
Authors: Abbasi Kiana , Ahangarkani Fatemeh , Badali Hamid 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Aspergillus species are capable of causing both invasive disease and chronic infections in immunocompromised patients or those with preexisting lung conditions. Management of superficial aspergillosis is a significant challenge owing to the frequent relapses and treatment failure, which may pose a potential risk, thereby gradually developing resistant species. So, necessitating the development of new antifungals with higher potency should be considered alternative strategies for efficient management of aspergillosis. We investigated the susceptibility patterns of Aspergillus isolates toward efinaconazole compared with various antifungal drugs. Antifungal susceptibility testing was performed according to the CLSI (M38) guidelines. Efinaconazole exhibited poor activity against azole-resistant A. fumigatus strains, A. niger sensu stricto, and A. tubingensis with GM MIC values of 3.62, 1.62, and 2 mg/l, respectively; however, surprisingly, it efficiently inhibited the growth of A. terreus sensu stricto, followed by wild-type A. fumigatus and A. flavus with GM MIC values of 0.29, 0.42, and 0.52 mg/l, respectively. Presumably, efinaconazole is inefficient in aspergillosis treatment due to the low susceptibility of A. niger sensu stricto, A. tubingensis, and azole-resistant A. fumigatus; however, it may be effective in treating superficial aspergillosis caused by susceptible A. fumigatus, A. terreus sensu stricto, and A. flavus. Differences in susceptibility patterns were observed between the generA. Awareness of the epidemiology of Aspergillus isolates and differences in antifungal susceptibility patterns around the globe may aid clinicians in choosing antifungal treatment regimens. However, studies are warranted to correlate these findings with clinical outcomes. Therefore, further studies are needed to determine how these findings may translate into in vivo efficacy.
P029 Synergic effect of deferoxamine combined with fluconazole against fluconazole-resistant Candida Spp. through inhibited Cek1 MAPK signaling pathway
Authors: An Lulu , Tan Jingwen , Wang Yuanyuan , Liu Siyu , Li Yongyong , Yang Lianjuan 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
The opportunistic fungal infections represent an increasing threat to humans with the increase of immunocompromised patients, in which Candida albicans is the most common fungal pathogen. Though fluconazole (FCA) is still the first line choice to treat C. albicans infections, several limitations such as an increase in drug resistance compromised its clinical application. This study proposes a combination therapy of deferoxamine (DFO) and FCA to overcome C. albicans resistance.

Methods
Checkerboard microdilution assay was used to determine the minimum inhibitory concentration (MIC) of DFO used alone and in combination with FCA against FCA-resistant Candida Spp. Spot assay and time-kill curves were used to investigate the cell viability and dynamic inhibitory effect. Hyphal formation was performed to investigate the underlying mechanism of DFO. Then, a murine model of cutaneous candidiasis was established to explore the in vivo synergistic activity of DFO and FCA.

Results
DFO combined with FCA showed synergistic antifungal activity against FCA-resistant C. albicans, with a fractional inhibitory concentration index (FICI) of 0.25. Moreover, DFO combined with FCA significantly inhibited the activity of C. glabrata cells, which is naturally insensitive to antifungal drugs. The spot assay and time-kill curve assay indicated that DFO can turn the fungistasis activity of FCA into fungicidal activity. Hyphal formation study showed the inhibition of hyphal induction of C. albicans. DFO combined with FCA also significantly inhibited the expression of Cek1 MAPK signaling pathway-related genes (CEK1 and CPH1) and adhesion-related genes (ALS1). In vivo data showed DFO combined with FCA significantly reduced the pustule, CFU numbers, and inflammatory cell infiltration of skin tissue.

Conclusion
Our results suggest that DFO combined with FCA inhibited the transformation of yeast-hyphae through Cek1 MAPK signaling pathway, resulting in reduced infectivity and resistance of C. albicans in vitro and in vivo, which may provide a new option for the treatment of cutaneous candidiasis.
P031 Post-antifungal effect of the combination of a nidulafungin with amphotericin B and fluconazole against fluconazole-susceptible and resistant Candida albicans
Authors: Aslani Narges 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
Invasive Candidiasis is a life-threatening condition that kills a large number of immunocompromised patients each year around the world. We used post-antifungal effect studies to analyze the activities of anidulafungin, as a clinically crucial antifungal drug, amphotericin B, and fluconazole (alone and in combinations) against FLC-susceptible and -resistant Candida albicans isolates obtained from the cancer patients.

Methods
We tested the phenomenon of post-antifungal effects (PAFEs) of fluconazole (FLC), amphotericin B (AMB), anidulafungin (AFG), and combinations of FLC + AFG, AFG + AMB, and FLC + AMB against 17 C. albicans isolates obtained from the oral cavity of cancer patients. Isolates that had not been exposed to antifungals, served as a control group. Colony counts were performed at 0, 2, 4, 6, and 24 h after a brief (1 h) antifungal exposure.

Results
The FLC had no detectable post-antifungal effect independent of antifungal concentration and resembled drug-free FLC (control). When all AMB and AFG were compared with FLC, significant variations in the post-antifungal effect were observed. Combining AFG and AMB with FLC resulted in effective activity compared to FLC alone. Combination regimens were rated as indifferent in general. Interestingly, low dosages of the AFG displayed increasing fungistatic action as it neared a fungistatic endpoint against C. albicans isolates (n = 17).

Conclusion
Our findings suggest that brief exposure to AFG, in combination with FLC and AMB, at low concentrations of the medicines utilized, could be effective in the evaluation and optimization of new dosage regimens to manage candidiasis. However, future research will look at the clinical utility of our findings.
P047 Comparative evaluation of disc diffusion and E-test with broth micro-dilution in susceptibility testing of amphotericin B, posaconazole, isuvuconazole, itraconazole against Rhizopus isolates of post COVID mucormycosis
Authors: Gupta Prashant , Hasan Mohd Saqib 
Published: September 2022

Abstract

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM

Objectives
To investigate and compare susceptibility pattern of Rhizopus isolates in post-COVID mucormycosis by disc diffusion (DD), E-test, and broth micro-dilution for amphotericin B, posaconazole. DD and BMD for isavuconazole and itraconazole.

Methods
All the isolates were identified by MALDI-ToF (Vitek MS). A total of 72 isolates of R. oryzae complex and 48 isolates of R. microsporus complex were selected. AFS by DD and E-test was done on non-supplemented Mueller Hinton Agar (MHA) and was compared with the Clinical Laboratory Standard Institute (CLSI M 38 A2) broth micro-dilution (BMD) method of AFS.

Results
The disk diffusion method for amphotericin B showed 91.6% agreement while E-test showed 97.2% agreement with broth micro-dilution. Disk diffusion method for posaconazole showed 93% agreement while E-test showed 97.2% agreement with broth micro-dilution. Disk diffusion method for ITZ and ISC showed 94.4% and 100% agreement respectively with broth micro-dilution.

Conclusion
CLSI method of DD promises to be an easier, reproducible, and cost-effective method of susceptibility testing, but this method must be interpreted with caution in the case of amphotericin B susceptibility testing. E-test correlates better than DD with BMD.