bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of corticosteroid-dependent eosinophilic interstitial nephritis
Authors: Tanabe Katsuyuki , Matsuoka-Uchiyama Natsumi , Mifune Tomoyo , Kawakita Chieko , Sugiyama Hitoshi , Wada Jun 
Published: December 2021

Abstract

Introduction:
Drug-induced acute interstitial nephritis (DI-AIN) is an important cause of acute kidney injury. In renal biopsy specimens, tubulitis with eosinophilic infiltration is suggestive of DI-AIN. Although corticosteroid therapy and discontinuation of the offending drug can improve renal dysfunction in most cases of DI-AIN, some patients experience AIN recurrence, leading to corticosteroid dependency. Corticosteroid-dependent eosinophilic interstitial nephritis presents a difficult dilemma in diagnosis and information regarding optimum management is limited.

Patient concerns:
A 25-year-old man, who received treatment with carbamazepine, zonisamide, valproate, and lacosamide for temporal lobe epilepsy, showed an increase in serum creatinine level from 0.98 to 1.29 mg/dL over a period of 6 months. Although he exhibited no symptoms, his serum creatinine level continued to increase to 1.74 mg/dL.

Diagnosis:
Renal biopsy revealed tubulitis and interstitial inflammatory infiltrates with eosinophils. Immunological and ophthalmological examinations showed no abnormal findings, and thus, his renal dysfunction was presumed to be caused by DI-AIN. Although oral prednisolone (PSL) administration (40 mg/d) and discontinuation of zonisamide immediately improved his renal function, AIN recurred 10 months later. The increase in PSL dose along with discontinuation of valproate and lacosamide improved renal function. However, 10 months later, recurrent AIN with eosinophilic infiltration was confirmed by further biopsy. The patient was therefore diagnosed with corticosteroid-dependent eosinophilic interstitial nephritis.

Interventions:
To prevent life-threatening epilepsy, carbamazepine could not be discontinued; hence, he was treated with an increased dose of PSL (60 mg/d) and 1500 mg/d of mycophenolate mofetil (MMF).

Outcomes:
MMF was well tolerated and PSL was successfully tapered to 5 mg/d; renal function stabilized over a 20-month period.

Lessons:
The presence of underdetermined autoimmune processes and difficulties in discontinuing the putative offending drug discontinuation are contributing factors to corticosteroid dependency in patients with eosinophilic interstitial nephritis. MMF may be beneficial in the management of corticosteroid-dependent eosinophilic interstitial nephritis by reducing the adverse effects related to high-dose and long-term corticosteroid use.
Therapeutic interventions in Osgood-Schlatter disease
Authors: Gaweł Eliza , Zwierzchowska Anna 
Published: December 2021

Abstract

Rationale:
The purpose of this case study was to identify factors of bilateral etiopathogenesis of Osgood-Schlatter disease (OSD) and those supporting the effectiveness of the therapeutic process in a 12-year-old elite female Olympic karateka.

Patient concerns:
The present case study concerns OSD female karateka who started her sport-specific training at the age of 4 years.

Diagnoses:
The results of subjective palpation by the orthopedic surgeon and objective medical examination using ultrasonography, wall slide test, magnetic resonance imaging, and body height and weight measurements were collected.

Interventions:
The therapeutic intervention for the athlete's knee joints lasted 20 months (5 stages). Physical therapy, kinesiotherapy, and pharmacological treatment were administered, and physical activity was gradually introduced.

Outcomes:
The developmental trajectory was uniform for body height and labile for body weight. OSD was diagnosed after the second growth spurt, and significant progression was reported during the subsequent height and weight gains and increased volume and intensity of sports training. The rate and dynamics of changes in the distance from the patellar ligament to the tibial apophysis were irregular, with dominance in the right knee with the highest rate of change (–3.3 mm) and twice the regression of the rate of change (–2.5 mm). The analyzed distance never exceeded the baseline value (5.5 mm), which was the case in the left knee. Return to sports competition was possible from the second month of therapy, in which kinesiotherapy and static stretching were the most effective. A relatively correct distance of the patellar ligament from the tibial apophysis was recorded at the time of stabilization of the body height and weight gain. No pathological changes were observed following OSD, and full recovery was observed.

Lessons:
In the case discussed in this study, growth spurt, the specificity of the sport practiced, and early specialization including high-volume and high-intensity training should be considered as factors causing OSD and its progression. Kinesiotherapeutic management and static stretching are crucial for the treatment of OSD. Quick return to sports competition was possible due to early therapeutic intervention, which could also lead to the absence of pathological changes in the tibial tubercle and the absence of recurrence of OSD.
Severe re-expansion pulmonary edema after chest tube insertion for the treatment of spontaneous pneumothorax
Authors: Song In-Hag 
Published: December 2021

Abstract

Rationale:
Re-expansion pulmonary edema (REPE) is a rare complication after chest tube insertion for the treatment of spontaneous pneumothorax. However, this complication can be life threatening when it occurs. Therefore, it is necessary to recognize REPE early and treat it appropriately. In the present study, we report a severe REPE case occurring after chest tube insertion in a patient with spontaneous pneumothorax.

Patient concerns:
A 27-year-old male patient visited out hospital with chest pain on the left, which had started a week ago. After diagnosed with pneumothorax and having chest tube insertion, the patient complained of sudden shortness of breath, persistent cough, foamy sputum, and vomiting.

Diagnosis:
Based on the symptoms and imaging findings, the patient was diagnosed as REPE.

Interventions:
After the condition of the patient deteriorated rapidly, he was transferred to intensive care unit and then mechanical ventilation and conservative treatment were performed after endotracheal intubation.

Outcomes:
After mechanical ventilation and conservative treatment in the intensive care unit, the symptoms and radiological findings improved, and then mechanical ventilation was weaned and the chest tube was removed from the patient. However, due to recurrent pneumothorax after removal of the chest tube, video assisted thoracoscopic surgery (VATS) wedge resection was performed. At 6 months post-operative follow up, he was well with normal radiological findings.

Lessons:
REPE occurs rarely, but once it does, it causes a serious condition that can be life-threatening. Therefore, patients with the risk factors related to it should receive a closed observation after chest tube insertion. Moreover, if REPE occurs, appropriate treatments should be carried out by recognizing it early.
Four-year follow up of macular intrachoroidal cavitation and chorioretinal atrophy
Authors: Abe Sanae , Iwase Takeshi 
Published: December 2021

Abstract

Rationale:
Macular intrachoroidal cavitation (ICC) is characterized by presence of a hyporeflective space beneath the unaltered retinal pigment epithelium (RPE) and is noted around the region of focal chorioretinal atrophy in eyes with pathologic myopia. The findings suggest that the patchy chorioretinal atrophy (PCA) progresses to ICC with time. However, there have been no reports describing long-term observational studies using OCT. We collected a case of PCA progression to macular ICC using OCT during a 4-year follow-up.

Patient concerns:
A 65-year-old woman presented with metamorphopsia and blurred vision in her left eye. Her best-corrected visual acuity (BCVA) was 20/20 and spherical equivalent refraction was –14.0 diopters in the left eye. Fundus examination revealed a white, well-defined PCA at the superonasal to the fovea which showed hypofluorescence determined by autofluorescence in the left eye. Sclera curved posteriorly at the superonasal to the fovea and the choroid was thickened at the area and ellipsoid zone (EZ) was disrupted in the area in OCT images. Additionally, another OCT images through the PCA showed a disappearance of the RPE–Bruch's membrane complex and a connection of blood vessels running from the sclera to the choroid.

Diagnoses:
PCA with macular ICC.

Interventions:
Observation.

Outcomes:
During 4-year follow up, the white patchy lesion and the hypofluorescence region gradually expanded. BCVA decreased with the expansion of the lesion and was 20/100 at the final visit. OCT through the fovea showed that the disorganized EZ expanded toward the ICC and the sensory retina of the fovea became thinner. Moreover, RPE–Bruch's membrane complex was not observed 3 years after the initial visit. During the follow-up period, the sensory retina was prominently displaced posteriorly to the ICC, though no obvious change was observed in the structure of the sclera.

Lessons:
In cases of PCA with macular ICC, the outer retina and RPE may initially atrophy, showing as an expansion of PCA, because the attachment between the inner retina and sclera may be weakened. This may result in the displacement of the retinal tissue into the space of macular ICC.
Radiosynthesis and biological evaluation of 18F-labeled bispecific heterodimer targeted dual gastrin-releasing peptide receptor and prostate-specific membrane antigen for prostate cancer imaging
Authors: Ye Shimin , Li Hongsheng , Hu Kongzhen , Li Li , Zhong Jiawei , Yan Qingsong , Wang Quanshi 
Published: December 2021

Objective
Approximately 5% of prostatic primary tumors and 15% of metastatic tumors were found to be prostate-specific membrane antigen (PSMA)-negative. Targeting gastrin-releasing peptide receptor (GRPR) has been shown to complement patients with PSMA-negative prostate cancer (PCa). Based on previous findings, simultaneously targeting PSMA and GRPR imaging may improve the diagnosis of PCa. In this study, we report the radiosynthesis and biological evaluation of a bispecific heterodimer of NOTA-GRPR-PSMA that targeted both PSMA and GRPR for extended PCa imaging.

Methods
NOTA-GRPR-PSMA was labeled using the Al18F-chelating one-step method. The competitive combination experiment and specific binding assay were performed in vitro using 22Rv1 (PSMA+) and PC-3 (GRPR+) cells. To determine the distribution and specificity in vivo, biodistribution and micro-PET/computed tomography of [18F]AlF-GRPR-PSMA were performed on mice bearing 22Rv1 or PC-3 tumors.

Results
[18F]AlF-GRPR-PSMA had a radiochemical purity of over 98% and demonstrated high stability in vivo and in vitro, with a LogD of −1.2 ± 0.05. Cell uptake and inhibition studies of [18F]AlF-GRPR-PSMA in 22Rv1 and PC-3 cells revealed bispecific GRPR and PSMA bindings. According to the biodistribution study and PET imaging, [18F]AlF-GRPR-PSMA was mainly excreted through the kidney. Tumor uptake was high in 22Rv1 tumor (10.1 ± 0.4 %ID/g) and moderate in PC-3 tumor (2.1 ± 0.6 %ID/g) 2 h p.i., whereas blocking studies significantly decreased the tumor uptake of 22Rv1 and PC-3.

Conclusion
[18F]AlF-GRPR-PSMA has the potential to simultaneously target PSMA and GRPR for PCa imaging.
Use of methadone as an alternative to morphine for chronic pain management: a noninferiority retrospective observational study
Authors: Moreira de Barros Guilherme Antonio , Baradelli Ricardo , Rodrigues Debora Garcia , Toffoletto Odaly , Domingues Flavia Seullner , Gayoso Maisa Vitoria , Lopes Alexandre , Barros Afiune Jorge , Nunes Guimarães Gabriel Magalhães 
Published: December 2021

Abstract

Introduction:
Chronic pain causes disability and is prevalent in the general population. Opioids are a part of a multimodal strategy for pain management. Methadone, a cheap and long-acting synthetic opioid, may represent an option for those who have limited access to the aforementioned class of analgesics. We aimed to provide a real-world evidence for the analgesic use of methadone, compared with morphine.

Methods:
We conducted a noninferiority, retrospective observational single center study of patients with chronic pain, managed with either methadone or morphine at an outpatient specialized clinic. We extracted data from the electronic health records of patients who underwent an active treatment between August 2012 and January 2020 and were examined for at least 2 consecutive medical visits, after the administration of one of the aforementioned drugs. Data were analyzed using a generalized additive model with random-effects mixed linear method to account for the individual-related, time-related, and drug-related variations. The numeric verbal scale (0–10) was used to assess the pain severity.

Results:
From the database of 3373 patients, we included 262 patients (175 methadone and 87 morphine). In an unadjusted analysis, methadone was superior to morphine, and the mean worst pain was 0.86 points lower (95% confidence interval, −1.29 to −0.43). Moreover, methadone was superior to morphine in the adjusted analysis, with the worst pain mean being 1.24 points lower. This provided evidence for the noninferiority of methadone than morphine.

Conclusion:
Methadone was superior to morphine in a 20% noninferiority margin for reducing worst pain.
The colon microcosm: a novel in vitro model to study Candida albicans colonisation of the human colon
Authors: Lenardon Megan 
Published: December 2021

Candida albicans colonises the gastro-intestinal (GI) tract of over 60% of the population. In severely ill or immune compromised patients, this fungus can escape the gut, disseminate through the body and cause systemic disease. Most research in the field has focused on defining traits that contribute directly to virulence; there are comparatively few studies which have addressed how C. albicans colonises and persists in the gut. Furthermore, such studies have typically been performed mouse models devoid of resident GI bacteria, completely neglecting the major impact of the local microbiota on GI colonisation. How, then, does C. albicans persist in the GI tract in the presence of the normal gut microbiota?
To address this question, a novel in vitro two-phase anaerobic fermentation system that simulates the human colon microenvironment has been developed. This “colon microcosm” supports the growth of human faecal microbiota in liquid anaerobic colon medium (phase 1) and C. albicans growth on agar plugs which are added to the medium to mimic the epithelial surface (phase 2). The impact of C. albicans upon the faecal microbiota is monitored by examining the planktonic phase (phase 1), whilst the effect of the microbiota on the growth of C. albicans is monitored after extracting C. albicans cells from the agar plugs (phase 2).
The results of assays carried out to validate the model will be presented, as will data from pilot studies which illustrate the potentially exploitable impact of the human GI microbiota from healthy individuals on C. albicans growth.
The first multi-omic interaction network in the human pathogen Candida glabrata provides novel insights into the virulence regulator, Hsp90
Authors: Crunden Julia , Haynes Ken , Diezmann Stephanie 
Published: December 2021

Candida glabrata-caused candidiasis is growing but treatments remain limited by paucity of drug targets, intrinsic azole resistance and increasing resistance to other drug classes. Drug resistance is one of numerous virulence traits regulated by the chaperone, heat shock protein 90 (Hsp90) in Candida albicans via its interactions with 5% of the genome. Hsp90 also regulates key drug resistance mechanisms in C. glabrata, but little else was known about Hsp90 in this organism. Therefore, CgHsp90 interactions were elucidated by genetic and proteomic methods.
A genetic network was produced by a chemical-genetic, synthetic-sick screen on a gene-deletion library covering 16% of the genome; whilst quantitative proteomics was undertaken by tandem mass tagging on wild-type cells. Both experiments were undertaken at 30°C, 37°C and 39°C and Hsp90 was perturbed using sub-lethal concentrations of Hsp90 inhibitor.
Efforts to identify Hsp90 interactors at these host-infection associated temperatures produced a genetic network of 68 genes and a protein network of 2298 proteins. Of these, 4 genes and 261 proteins interacted with Hsp90 at all three temperatures, indicating a core Hsp90 interaction network. Intriguingly, both networks had enrichment for the “antibiotic biosynthesis” GO term. Two genes, BCY1 and MCM16, were found to interact with Hsp90 at multiple temperatures in both networks. These data indicate the divergence of Hsp90 networks between C. glabrata and its close relatives and offer important targets for further research.
Presented here is the first multi-omic interaction network in C. glabrata, focused on the virulence and drug resistance regulator, Hsp90.
In silico screening leads to novel scaffolds with both antifungal and anti-NLRP3 inflammasome activity
Authors: Lowes David , Al-waqfi Rand , Hevener Kirk , Peters Brian 
Published: December 2021

Due to structural similarities that exist between established inhibitors of the NLRP3-inflammasome, sulfonylureas Glyburide and MCC-950, and herbicidal-sulfonylureas, that specifically target fungal acetohydroxyacid synthase (AHAS), we sought to determine the potential for compounds to block both inflammation and inhibit fungal growth.
In silico screening of ∼250,000 compounds was used to identify a prioritized list of chemical structures capable of inhibiting both targets. Prioritization of the top 1% of scores identified ∼70 compounds with a diverse set of scaffolds for testing in vitro. Selected hits were used to assess anti-inflammatory function in a THP-1 challenge model with LPS+ATP and resulting IC50 values were obtained. MIC and hyphal-growth assays were conducted to determine potential antifungal activity using media depleted of branched chain amino acids isoleucine and valine, to confirm on target AHAS inhibition.
Identification of hits that exhibited low micromolar activity for NLRP3 and AHAS inhibition were selected for SAR study. In vitro testing of the analogs along with molecular docking led to increased knowledge for lead optimization of the potential hits.
In silico screening has resulted in IC50 (IL-1β release) and MIC50 (fungal growth) values with low μM potency against several Candida species. In vivo validation will further confirm the potential of the scaffolds for further synthetic-modification for the rationale design of novel dual-purpose drugs
Azole uptake in Candida auris is strongly correlated with drug resistance
Authors: Esquivel Brooke , White Theodore C. 
Published: December 2021

Analyses of fluconazole uptake in clinical isolates of C. auris, with wide ranging drug resistance profiles, has revealed interesting differences within the species as well as major distinctions from other yeast species. We previously proposed that prevention of drug uptake is a potential mechanism of drug resistance and our C. auris data provide further support for this.
We developed an assay using radio-labeled fluconazole to measure intracellular azole accumulation in fungal cells. The assay is performed under glucose-replete conditions to inhibit ATP-dependent efflux. A comparative study measuring fluconazole uptake in 63 C. auris isolates as well as a panel of other species such as C. albicans, S. cerevisiae, C. glabrata, C. krusie, C. lusitanea, C. tropicalis, and C. dublinienses revealed striking C. auris phenotypes that we have not seen in other fungal species.
There is a strong correlation between fluconazole resistance and reduced drug uptake in C. auris. Fluconazole-resistant C. auris isolates had reduced levels of intracellular fluconazole accumulation compared to susceptible isolates. Drug-resistant C. auris isolates had the lowest drug accumulation of any of the yeast species tested. Fluconazole-susceptible C. auris isolates had dramatically increased fluconazole accumulation compared to the resistant isolates as well as when compared to other yeast species.
Of the 63 C. auris isolates, 28 of 32 (∼88%) resistant isolates had extremely low fluconazole uptake, whereas 15 of 18 (∼83%) susceptible isolates had high fluconazole uptake. This association between reduced drug uptake and resistance could be a C. auris-distinctive mechanism of drug resistance.
Novel antifungal activity of Q-Griffithsin, a broad-spectrum antiviral lectin
Authors: Nabeta Henry , Kouokam Joseph C , Lasnik Amanda , Fuqua Joshua , Palmer Kenneth E 
Published: December 2021

Background
There is a rising global trend in candida strains with high resistance to fluconazole and other antifungal drugs, hence the need for novel agents. Here, we investigated the anti-Candida activity of Q-Griffithsin (Q-GRFT), a lectin naturally produced by the red-sea algae, Griffithsia spp.

Methods
To assess in vitro growth inhibitory activity, C. albicans was incubated with Q-GRFT on agar plates and in broth media. We investigated GFP-bound Q-GRFT’s ability to adhere to C. albicans using fluorescence microscopy and fluorescence intensity assessments. To demonstrate in vivogrowth inhibitory activity, CBA/J mice were treated per vaginam with Q-GRFT followed by challenge with C. albicans, and fungal burden determined following vaginal lavage.

Results
Wild type fluorescently labeled Q-GRFT displayed higher fluorescence than the lectin-binding site deficient variant following incubation with C. albicans. Q-GRFT localized around the fungal cells and bound to α-mannan in the cell wall. Q-GRFT significantly inhibited C. albicans growth in broth and on agar plates, disrupted the integrity of the cell wall, and induced ROS formation. The lectin significantly inhibited the growth of C. glabrata, C. parapsilosis and C. krusei, with modest activity against C. auris CDC388 and C. auris CDC389 strains in vitro. Topical treatment resulted in a lower fungal burden compared to the vehicle control group in vaginal candidiasis.

Conclusion
Q-GRFT binds to and inhibits C. albicans growth both in vitro and in vivo. Further studies are needed to establish the mechanism of growth inhibition.
Investigation of the interaction of keratinocytes and Candida species
Authors: Ádám Novák , Erik Zajta , Máté Csikós , Csaba Vágvölgyi , Attila Gácser 
Published: December 2021

Our skin provides immunological protection against several pathogens. Skin epithelial cells respond to microbial stimuli in various ways, such as through the production of antimicrobial peptides or secretion of cytokines, although phagocytosis of potentially evading microbes was also reported.
Relatively little is known about how skin keratinocytes differentiate between the presence of pathogenic and commensal fungi. In this project, we aimed to investigate how human keratinocytes interact with different Candida species, as common colonizers of the skin. While C. albicans is a common cause of cutaneous candidiasis, C. parapsilosisis rarely associated with this disease.For the experimentshuman skin keratinocyte cell lines (HaCaT, HPV-KER)were applied andchallengedwith C. albicans (SC5314 and WO1 strains) and C. parapsilosis (GA1 and CLIB214 strains)strains.We aimedto determine the extent to which C. albicans and C. parapsilosis damage human keratinocytes, their attachment to host cells, the keratinocytes’ ability to internalize these fungi and to examinecytokine production in response to stimuli.
Our results suggest that C. albicans causes significantly more damage to human keratinocytes than C. parapsilosis and the HPV-KER cell line was more susceptibleto the infection. In both HaCaT and HPV-KER cells, the production of IL-6, IL-8, and CCL5 increased primarilyafter C. albicans infection. Based on the adhesion studies, there was a low degree of association in case of C. parapsilosis GA1 and CLIB214 compared to C. albicans SC5314 and WO1.