bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased Lymphocytic Bronchitis Severity in the Era of Azithromycin Prophylaxis
Authors: Santos Jesse , Hays Steven R. , Golden Jeffrey A. , Calabrese Daniel R. , Kolaitis Nicholas , Kleinhenz Mary Ellen , Shah Rupal , Estrada Aida Venado , Leard Lorriana E. , Kukreja Jasleen , Singer Jonathan P. , Greenland John R. 
Published: August 2023

Background.
Large-airway lymphocytic inflammation (LB), assessed on endobronchial biopsies, has been associated with acute cellular rejection and chronic lung allograft dysfunction (CLAD). Azithromycin (AZI) prophylaxis has been used to prevent airway inflammation and subsequent CLAD, with inconsistent results. We hypothesized that AZI prophylaxis would be associated with reduced LB, changes in bronchoalveolar lavage (BAL) immune cell populations, and improved CLAD-free survival.

Methods.
We compared frequencies of LB from endobronchial biopsies before (N = 1856) and after (N = 975) protocolized initiation of AZI prophylaxis at our center. LB was classified as none, minimal, mild, or moderate by histopathologic analysis. LB grades were compared using ordinal mixed-model regression. Corresponding automated BAL leukocyte frequencies were compared using mixed-effects modeling. The effect of AZI prophylaxis on CLAD-free survival was assessed by a Cox proportional hazards model adjusted for age, sex, ethnicity, transplant indication, and cytomegalovirus serostatus.

Results.
Biopsies in the pre-AZI era had 2-fold increased odds (95% confidence interval, 1.5-2.7; P < 0.001) of higher LB grades. LB was associated with BAL neutrophilia in both eras. However, there was no difference in risk for CLAD or death between AZI eras (hazard ratio 1.3; 95% confidence interval, 0.7-2.0; P = 0.45).

Conclusions.
Decreased airway inflammation in the era of AZI prophylaxis may represent a direct effect of AZI therapy or reflect other practices or environmental changes. In this cohort, AZI prophylaxis was not associated with improved CLAD-free survival.
Effect of β-Nicotinamide Adenine Dinucleotide on Acute Allograft Rejection After Rat Lung Transplantation
Authors: Ehrsam Jonas P. , Chen Jin , Haberecker Martina , Arni Stephan , Inci Ilhan 
Published: August 2023

Background.
Acute rejection is still a major limitation for a successful outcome in lung transplantation. Since β-nicotinamide adenine dinucleotide (NAD+) has been shown to have various immunomodulatory properties on the innate and adaptive immune system, we evaluate here a potential protective effect of NAD+ against acute lung rejection.

Methods.
Rat single-lung transplantation was performed in 2 groups (n = 8 per group), using Brown-Norway donors and major histocompatibility complex–mismatched Lewis recipients. Recipients of the NAD+ group received 1000 mg/kg NAD+ intraperitoneally before transplantation and daily thereafter until euthanasia, whereas the control group received saline solution. At autopsy on day 5, blood samples were analyzed and the lung allograft was assessed by bronchioalveolar lavage, histology, and immunochemistry.

Results.
The NAD+ group maintained an intact compliant lung tissue, a strong trend of lower acute cellular rejection (A3 versus A3-A4) and significantly less lymphocytic bronchiolitis (B0-B2R versus B1R-Bx). In addition, a trend of fewer alveolar CD68+ macrophages and significantly fewer interstitial CD163+ macrophages was observed. Bronchoalveolar lavage in the NAD+ group showed significantly fewer proinflammatory cytokines interleukin (IL)-6, IL-13, TNFα, and a protective IL-6/IL-10-ratio. In blood samples, we observed significantly fewer neutrophils, and proinflammatory GRO/KC in the NAD+ group.

Conclusions.
NAD+ might be a promising substance in prevention of acute allograft rejection in lung transplantation.
Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation
Authors: Thorsen Inga Strand , Bleskestad Inger Hjørdis , Åsberg Anders , Jonsson Grete , Skadberg Øyvind , Heldal Kristian , Gøransson Lasse Gunnar 
Published: August 2023

Background.
Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels.

Methods.
Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013.

Results.
Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival.

Conclusions.
In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.
Alzheimer’s Behavioral and Psychiatric Burden in Saudi Arabia
Authors: Tayeb Haythum O. , Butt Nadeem S. , Khallaf Roaa , Yaghmoor Bassam , Basheikh Mohammed A. , Alamri Sultan H. , Baduwailan Abrar O. , Alzaben Faten , Abdulghaffar Haifa K. , Koenig Harold G. 
Published: August 2023

Background:
The burden of behavioral and psychiatric symptoms in dementia (BPSD) has not been characterized in Saudi patients with Alzheimer disease (AD). Moreover, the Saudi version of the Neuropsychiatric Inventory (SNPI) has not been validated.

Objectives:
The purpose of this study was to validate the SNPI and describe frequency and determinants of BPSD in Saudi AD patients.

Methods:
The SNPI and BEHAVE-AD instruments were administered to community-dwelling Saudi AD patients and their caregivers.

Results:
The sample size was 192. The first 59 constituted the validation cohort. Cronbach alpha of the SNPI and BEHAVE-AD were 0.91 and 0.79, respectively. There were significant correlations between: (1) the total SNPI and BEHAVE-AD scores (r=0.84, P<0.001); (2) analogous SNPI and BEHAVE-AD symptom subscores (P<0.05); (3) SNPI and BEHAVE-AD caregiver distress (F=22.6, P<0.001). Inter-rater reliability of the SNPI was excellent (kappa=0.74). Ninety percent of patients experienced 4 SNPI symptoms or more. Patients with stroke and prior psychiatric history were most likely to experience BPSDs. The most common symptom was apathy (82%). Caregiver distress was determined by the total NPI score and impulsiveness subscale score.

Conclusions:
The SNPI is valid and reliable for assessing BPSD in Saudi AD patients. Longitudinal studies of BPSDs in Saudi specialized dementia clinics are needed.
Electroconvulsive Therapy in Heart Transplant Patients
Authors: Ketcham Evan , Glass Oliver M. , Hermida Adriana P. 
Published: August 2023

Abstract
Patients with heart disease are at an increased risk of depression. Electroconvulsive therapy (ECT) is a highly effective treatment for severe depressive episodes. However, ECT may increase the risk for adverse outcomes in certain patients because of changes in blood pressure and heart rate secondary to an initial parasympathetic surge followed by a sympathetic surge and peripheral catecholamine release. In post–cardiac transplant patients, these acute hemodynamic changes on a denervated heart may bring clinical challenges. The available data on ECT in heart transplant patients are limited. The authors of this article present a summary of the available literature relating to ECT in heart transplant patients.
The authors performed a literature search of 6 online databases yielding 6 English-language case reports of ECT in cardiac transplant patients. All patients experienced changes in hemodynamic variables during and immediately after ECT, ranging from moderate decrease in blood pressure to extreme hypertension. The cases did not report any serious cardiac complications during the course of ECT. In the 5 patients whose psychiatric responses to treatment were detailed, all had improvement in their depressive symptoms. Electroconvulsive therapy may be considered for severe cases of depression in patients with a history of cardiac transplant, but the potential benefit of ECT needs to be weighed against risks. In the limited number of cases reported in the literature, ECT seems to have been relatively safe and effective.
Electroconvulsive Therapy Credentialing for Psychiatrists—Review of Required Standards Across States and Territories in Australia
Authors: Purushothaman Subramanian , Simpson Brett , Hussain Salam , Loo Colleen K. , Gill Shane , Chamoli Suneel , Weiss Alan , Sarma Shanthi , Fitzgerald Paul B. , Fasnacht Matthew , Gandhi Ashu 
Published: August 2023

Abstract
Electroconvulsive therapy (ECT) is a complex medical procedure, the delivery of which requires specialist knowledge and skills. We reviewed the standards required for ECT credentialing in different jurisdictions in Australia. We reviewed the Chief Psychiatrist guidelines and statewide policy standards on ECT and focused on standards required for initial credentialing and ongoing privileging in ECT. We compared the credentialing requirements within these documents with the standards specified in the Royal Australian and New Zealand College of Psychiatrists professional practice guideline for ECT. Most of the jurisdictions had specific standards for initial credentialing and maintenance of this credentialing; however, there was significant variance in the credentialing process and standards required. It would be useful to have a minimum standard for credentialing for ECT psychiatrists and prescribers. This standard would be relevant for practice of ECT internationally. States and territories would have the responsibility for implementation of these standards. Appropriate training and establishing good clinical governance processes are essential to the provision of high quality ECT.
Identification of NpdA as the protein forming the surface layer in Paracidovorax citrulii and evidence of its occurrence as a surface layer protein in diverse genera of the Betaproteobacteria and Gammaproteobacteria
Authors: Gajbhiye Shabda , Gonzales Erin D. , Toso Daniel B. , Kirk Natalie A. , Hickey William James 
Published: August 2023

The phytopathogen Paracidovorax citrulli possesses an ortholog of a newly identified surface layer protein (SLP) termed NpdA but has not been reported to produce a surface layer (S-layer). This study had two objectives. First, to determine if P. citrulli formed a NpdA-based S-layer and, if so, assess the effects of S-layer formation on virulence, production of nanostructures termed nanopods, and other phenotypes. Second, to establish the distribution of npdA orthologs throughout the Pseudomonadota and examine selected candidate cultures for physical evidence of S-layer formation. Formation of a NpdA-based S-layer by P. citrulli AAC-001 was confirmed by gene deletion mutagenesis (ΔnpdA), proteomics, and cryo-electron microscopy. There were no significant differences between the wild type and mutant in virulence assays with detached watermelon fruit. Nanopods contiguous with S-layers of multiple biofilm cells were visualized by transmission electron microscopy. Orthologs of npdA were identified in 62 Betaproteobacteria species and 49 Gammaproteobacteria species. In phylogenetic analyses, NpdA orthologs largely segregated into distinct groups. Cryo-electron microscopy imaging revealed a NpdA-like S-layer in all but one of the 16 additional cultures examined. We conclude that NpdA represents a new family of SLP, forming an S-layer in P. citrulli and other Pseudomonadota. While the S-layer didn’t contribute to virulence in watermelon fruit, a potential role of the P. citrulli S-layer in another dimension of pathogenesis cannot be ruled out. Lastly, formation of cell-bridging nanopods in biofilms is a new property of S-layers; it remains to be determined if nanopods can mediate intercellular movement of materials.
Tract-based disconnection induced by WMH in patients with minor stroke is related to long-term post-stroke cognition
Authors: Lopes Renaud , Kuchcinski Grégory , Dondaine Thibaut , Duron Loïc , Mendyk Anne-Marie , Hénon Hilde , Cordonnier Charlotte , Pruvo Jean-Pierre , Bordet Régis , Leclerc Xavier 
Published: August 2023

AbstractBackgroundOver a third of minor stroke patients will suffer from post-stroke cognitive impairment (PSCI) but there are no validated tools to clearly identify at-risk patients in the early phase. We aimed to investigate the short and long-term cognitive decline using disconnection features from infarct and white matter hyperintensities (WMH) in first-ever minor ischemic stroke patients.MethodsFirst-ever minor ischemic stroke patients (NIHSS≤7) were prospectively followed-up at 72-hour, 6- and 36-month post-stroke with cognitive tests and conventional brain MRI. Infarct and WMH volumes were semi-automatically evaluated on DWI and FLAIR sequences respectively. Bayesian models using tract-based structural disconnection were used to estimate the remote pathological effects of cerebral infarct and/or WMH. The disconnection approach was compared to features extracted from cerebral infarct and WMH volumes and locations. All lesion-based features were compared between patients with and without cognitive impairment at 6- and 36-month post-stroke. The potential association between the features and cognitive domains alterations was assessed by canonical correlation analyses. All statistical analyses were corrected for age, education and multiple comparisons.Results105 patients (female, 31%) with a mean (± SD) age of 63 ± 12 years were enrolled. Infarct volume was 10.28 ± 17.10 cm3 and involved the middle cerebral artery territory in 83% of patients. The burden of WMH was higher within frontal periventricular white matter. Infarct-based features showed no significant relationship with 6 and 36-month PSCI. However, a WMH disconnection factor involving the commissural and frontal tracts was associated with 6- and 36-month PSCI, particularly in executive/attention, language and visuospatial domains. Memory domain alterations were associated with higher WMH burden in right temporal regions.ConclusionsWMH-induced disconnectivity may predict short and long-term PSCI in minor ischemic stroke. These neuroimaging features extracted from routine MR sequences could help identifying at-risk patients to test future rehabilitation interventions.
EasyFlow: An open source, user friendly cytometry analyzer with graphic user interface (GUI)
Authors: Ma Yitong , Antebi Yaron 
Published: August 2023

AbstractFlow cytometry enables quantitative measurements of fluorescence in single cells. The technique was widely used for immunology to identify populations with different surface protein markers. More recently, the usage of flow cytometry has been extended to additional readouts, including intracellular proteins and fluorescent protein transgenes, and is widely utilized to study development, systems biology, microbiology, and many other fields. A common file format (FCS format, defined by International Society for Advancement of Cytometry (ISAC)) has been universally adopted, facilitating data exchange between different machines. A diverse spectrum of software packages have been developed for analysis of flow cytometry data. However, those are either 1) costly proprietary softwares, 2) open source packages with prerequisite installation of R or Python and sometimes require users to have experience in coding or 3) online tools that are limiting for analysis of large data sets. Here we present EasyFlow, an open source flow cytometry analysis GUI based on Matlab or Python, that can be installed and run locally cross-platform-ly (Windows and MacOS), without prerequisite user having previous knowledge on coding. The python version (EasyFlowQ) is also developed on a popular plotting framework (Matplotlib) and modern user interface (UI) toolkit (Qt), allowing more advanced users to customize and keep contributing to the software, as well as its tutorials. Overall, EasyFlow serves as a simple-to-use tool for inexperienced users with little coding experience to use locally, as well as a platform for advanced users to further customize for their own needs.
Synthetic rescue of XPC phenotype via PIK3C3 downregulation
Authors: Kobaisi Farah , Sulpice Eric , Nasrallah Ali , Fayyad-Kazan Hussein , Rachidi Walid , Gidrol Xavier 
Published: August 2023

AbstractXeroderma Pigmentosum C is a dermal hereditary disease. It is caused by a mutation in the DNA damage recognition protein XPC that belongs to the Nucleotide excision repair pathway. XPC patients exhibit a photosensitive phenotype and fail to repair UV induced DNA lesions leading to their accumulation and ultimate conversion to mutations and carcinomas. In an attempt to normalize this phenotype, we screened a library of siRNAs targeting the human kinases, given their role in different DNA repair pathways. WT and XPC immortalized patient fibroblasts were transfected with the library then irradiated with UVB to induce DNA damage. XPC phenotypic reversal was monitored by the quantification of decreased photosensitivity and increased DNA damage repair. Out of the 1292 kinase siRNAs tested, twenty-eight were selected cellular survival compared to cells transfected with non-targeting siRNA in XP-C irradiated cells. Out of the selected hits, two kinases, PIK3C3 and LATS1, induce more than 20% repair of 6-4PP DNA lesions. The down regulation of autophagy-related protein PIK3C3 alone had an exclusive photo protective effect on XP-C irradiated cells validated these effects also on primary XP-C patient fibroblasts and CRISPR-Cas9 generated XPC-KO keratinocytes. PIK3C3 knock down in XP-C cells ameliorated in UVB dose response analysis, decreased apoptosis and lowered phosphorylation of P53 with no effect on proliferation. More importantly, PIK3C3 knock down induced an increase in UVRAG expression, a previously reported cDNA conveying lower photosensitivity in XP-C cells. Attempts to improve the XPC photosensitive and deficient repair phenotype using PIK3C3 inhibitors could thus pave a way for new therapeutic approaches delaying or preventing tumor initiation.
In silico thermodynamic evaluation of the effectiveness of RT-LAMP primers to SARS-CoV-2 variants detection
Authors: Miranda Pâmella , Alves Pedro A. , do Monte-Neto Rubens L. , Weber Gerald 
Published: August 2023

AbstractViral mutations are the primary cause of mismatches in primer-target hybridisation, affecting the sensibility of molecular techniques, potentially leading to detection dropouts. Despite its importance, little is known about the quantitative effect of mismatches in primer-target hybridisation. We use up-to-date and highly detailed thermodynamic model parameters of DNA mismatches to evaluate the sensibility to variants of SARS-CoV-2 RT-LAMP primers. We aligned 18 RT-LAMP primer sets, which were underwent clinical validation, to the genomes of Wuhan strain (ws), 7 variants and 4 subvariants, and calculated hybridisation temperatures allowing up to three consecutive mismatches. We calculate the coverage when the mismatched melting temperature falls by more than 5°C in comparison to the matched alignments. If no mismatches are considered, the average coverage found would be 94% for ws, falling the lowest value for Omicron: 84%. However, considering mismatches the coverage is much higher: 97% (ws) to 88% (Omicron). Stabilizing mismatches (higher melting temperatures), account for roughly 1/3 of this increase. The number of primer dropouts increases for new each variant, however the effect is much less severe if mismatches are considered. We suggest using melting temperature calculations to continuously assess the trend of primer dropouts.
Cryo-EM structure of DDM1-HELLS chimera bound to nucleosome reveals a mechanism of chromatin remodeling and disease regulation
Authors: Nartey Wilson , Goodarzi Aaron A. , Williams Gareth J. 
Published: August 2023

AbstractHuman HELicase, Lymphoid Specific (HELLS), and plant homolog Deficient in DNA Methylation 1 (DDM1), belong to a distinct class of chromatin remodelers that play important roles in DNA repair, transcription, and maintenance of DNA methylation in heterochromatin. HELLS also promotes the growth of hard-to-treat cancers including glioblastoma and hepatocellular carcinoma. Here, we identify an auto-inhibitory HELLS N-terminal coiled-coil, unravelling a long-standing question of HELLS inactivityin vitro. Using cryo-EM, we determine the 3.5 Å structure of an active DDM1-HELLS chimera in complex with a nucleosome. The structure reveals that a HELLS-specific insertion in the ATPase lobe 2 interacts with the nucleosome acidic patch to enhance chromatin remodeling. At the C-terminus, we resolve a unique motif, and disease hot spot, that binds and stabilizes the ATPase motor of the HELLS family of remodelers. Finally, we provide mechanistic insights for how post-translational modifications in the motor domain and midloop could modulate HELLS activity to regulate cancer stem cell state.
Genomic and epidemiological evidence for the emergence of a putativeL. donovani/L. infantumhybrid with unusual epidemiology in Northern Italy
Authors: Bruno F. , Castelli G. , Li B. , Reale S. , Carra E. , Vitale F. , Scibetta S. , Calzolari M. , Varani S. , Ortalli M. , Franceschini E. , Gennari W. , Rugna G. , Späth G.F. 
Published: August 2023

AbstractLeishmania (L.) infantumis the main causative agent of animal and human leishmaniasis in the Mediterranean basin. Despite its clinical significance, little is known on the genetic diversity ofL. infantumparasites circulating in Italy. Here, we apply a comparative genomics approach on sevenL. infantumisolates from different hosts (human, dog, cat, marten) and geographic regions (Emilia-Romagna, Sicily, Sardinia) as a first attempt to explore the breadth of parasite genetic heterogeneity in Italy. We revealed important genome instability at karyotype levels, with each isolate presenting a unique aneuploidy profile. Read depth analysis further identified strain-specific changes in gene dosage, which affected important virulence factors most of which are encoded by multi-copy gene arrays, such as amastins or surface antigen-like proteins. SNP-based clustering analysis of these genomes together with over 80 publicly availableL. infantumandL. donovanigenomes placed the Italian isolates into three geographically distinct clusters, with two isolates grouping with Spanish strains, two isolates grouping with Tunisian strains, and three isolates clustering with putativeL. infantum/L. donovanihybrids isolated in Cyprus. As judged by microsatellite profiling of 73 isolates from dogs, sand flies and VL cases, these hybrid isolates are representative of a sub-population of parasites circulating in northeastern Italy that preferentially infects humans, but not dogs. In conclusion, our data uncover a remarkable heterogeneity ofL. infantumisolates that indicates different geographic origin, including a novel hybrid-like genotype associated with an unusual infection pattern, placing Italy at the crossroad ofLeishmaniainfection in the Mediterranean region.