bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utility of Semistructured Interview and Scales to Assess Withdrawal Syndromes With Dose Reduction or Discontinuation of Selective Serotonin Reuptake Inhibitors or Serotonin Norepinephrine Reuptake Inhibitors
Authors: Cosci Fiammetta , Romanazzo Sara , Mansueto Giovanni , Rontani Petra , Levitan Michelle N. , Halkjœr-Lassen Roseane D. , Quagliato Laiana A. , Nakamura Tomoyuki , Uematsu Ken , Nardi Antonio E. , Oe Misari , Chouinard Virginie-Anne , Chouinard Guy 
Published: December 2021

Abstract

Background
Withdrawal syndromes can occur after dose reduction or discontinuation of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Few measurement instruments are available to assess them: Diagnostic Clinical Interview for Drug Withdrawal 1–New Symptoms of SSRI and SNRI (DID-W1) and Discontinuation Emergent Signs and Symptoms (DESS) checklist. We assessed their interrater reliability, verified the percent agreement between the two, and tested DESS sensitivity and specificity on the basis of the diagnoses formulated via the DID-W1.

Methods
One-hundred thirty-four subjects who referred for withdrawal at 3 outpatient facilities were enrolled and assessed via the DESS and the DID-W1. Percent agreement and Cohen κ were calculated to measure DID-W1 and DESS interrater reliability, as well as the agreement between DID-W1 and DESS items. Sensitivity and specificity of DESS were derived from the identification of true-positive, false-negative, true-negative, and false-positive on the DID-W1.

Results
Both tools showed excellent interrater reliability (DID-W1 Cohen κ = 0.958; DESS Cohen κ = 0.81–1). The degree of agreement between DID-W1 and DESS items was poor or fair (Cohen κ < 0.40) for some items and moderate (Cohen κ = 0.41–0.60) for others. Sensitivity and specificity of DESS were 0.937 (true-positive = 60, false-negative = 4) and 0.285 (true-negative = 20, false-positive = 50), respectively.

Conclusions
DID-W1 was a reliable method to identify and diagnose withdrawal syndromes. The DESS checklist showed to be a useful tool for detecting withdrawal SSRI/SNRI symptoms when the aim is to achieve high sensitivity to identify true positives.
Surgical Outcomes of Pancreatectomy with Resection of the Portal Vein and/or Superior Mesenteric Vein and Jejunal Vein for Pancreatic Head Cancer
Authors: Nagakawa Yuichi , Jang Jin-Young , Kawai Manabu , Kim Song Cheol , Inoue Yosuke , Matsuyama Ryusei , Heo Jin Seok , Honda Masayuki , Sugiura Teiichi , Ohtsuka Masayuki , Mizuno Shugo , Kwon Wooil , Uemura Kenichiro , Han Ho-Seong , Sugimoto Motokazu , Okano Keiichi , Nakamura Masafumi , Wada Keita , Kumamoto Yusuke , Osakae Hiroaki , Tsuchida Akihiko , Yoon Yoo-Seok , Park Joon Seong , Yamaue Hiroki , Endo Itaru 
Published: December 2021

Objective:
The aim of this study was to investigate the safety and survival benefits of portal vein and/or superior mesenteric vein (PV/SMV) resection with jejunal vein resection (JVR) for pancreatic ductal adenocarcinoma (PDAC).

Summary Background Data:
Few studies have shown the surgical outcome and survival of pancreatic resection with JVR, and treatment strategies for patients with PDAC suspected of jejunal vein (JV) infiltration remain unclear.

Methods:
In total, 1260 patients who underwent pancreatectomy with PV/ SMV resection between 2013 and 2016 at 50 facilities were included; treatment outcomes were compared between the PV/SMV group (PV/ SMV resection without JVR; n = 824), PV/SMV-J1 V group (PV/SMV resection with first jejunal vein resection; n = 394), and PV/SMV-J2,3 V group (PV/SMV resection with second jejunal vein or later branch resection; n = 42).

Results:
Postoperative complications and mortality did not differ between the three groups. The postoperative complication rate associated with PV/ SMV reconstruction was 11.9% in PV/SMV group, 8.6% in PV/SMV-J1 V group, and 7.1% in PV/SMV-J2,3V group; there were no significant differences among the three groups. Overall survival did not differ between PV/SMV and PV/SMV-J1 V groups (median survival; 29.2 vs 30.9 months, P = 0.60). Although PV/SMV-J2,3 V group had significantly shorter survival than PV/SMV group who underwent upfront surgery (P = 0.05), no significant differences in overall survival of patients who received preoperative therapy. Multivariate survival analysis revealed that adjuvant therapy and R0 resection were independent prognostic factors in all groups.

Conclusion:
PV/SMV resection with JVR can be safely performed and may provide satisfactory overall survival with the pre-and postoperative adjuvant therapy.
Investigation of the MFS drug transporter family in Candida parapsilosis using CRISPR-Cas9
Authors: Zhao Fang , Butler Geraldine 
Published: December 2021

The function of specific transporters is a key feature underlying drug resistance in Candida species. Drug transporters fall into two main classes – ATP-binding cassette (ABC) transporters, and the major facilitator superfamily (MFS) transporters. Some members of the drug/H (+) antiporter (DHA1) of the MFS superfamily have been shown to function as multidrug transporters. We targeted 16 genes belonging to five families that compose one branch of the DHA1 transporter group. These include MDR1/FLR1, associated with multidrug resistance in C. albicans (3 members); TPO4, associated with polyamine transport (1 member); NAG3/4, associated with transport of N-acetyl glucosamine (2 members); TPO2/3, associated with polyamine transport (1 member); and TPO1/FLU1, possibly associated with fluconazole resistance (9 members). We used CRISPR-Ca9 based gene editing to explore the function of of the five families in C. parapsilosis.
All 16 members were individually disrupted by introducing stop codons in the first third of the open reading frames (editing), or by deleting the whole gene. In addition, members of each family were disrupted together, including all 9 members of the TPO1/FLU1 family. CPAR2_603010, CPAR2_207540, and CPAR2_301760 all belonged to the MDR1 family. Editing CPAR2_603010 conferred sensitivity to fluconazole and voriconazole, though disrupting the other two genes had no effect. The azole sensitivity of the CPAR2_603010 edited strain was reverted by introducing the wild type sequence. Disrupting CPAR2_603010 or CPAR2_301760 individually did not affect sensitivity to 4-nitroquinoline 1-oxide. However, the double disruptant was sensitive. Disrupting CPAR2_300760, a member of the TPO1/FLU1 family, resulted in sensitivity to mycophenolic acid. Whole genome sequencing analysis of a strain in which all nine TPO1 genes were disrupted revealed that few off-target effects introduced by the CRISPR-Cas9 system, as few unexpected changes were found after eight rounds of transformation.
Exploration of anti EFG1 locked nucleic acid gapmers to control Candida albicans filamentation
Authors: Araújo Daniela , Mil-Homens Dalila , Jørgensen Per Trolle , Fialho Arsénio M. , Wengel Jesper , Henriques Mariana , Silva Sónia 
Published: December 2021

Introduction:
Antisense oligonucleotides (ASOs) have been successfully utilized to silence gene expression for the treatment of many genetic human diseases, and particularly the locked nucleic acid (LNA) chemical modification is extensively used with this propose. However, LNA-modified ASOs have never been exploited for controlling virulence genes of Candida.
EFG1is an important determinant of virulence that is involved in the switch from yeast to filamentous forms in C. albicans. Thus, our main goal was to explore LNA antisense gapmers for controlling EFG1gene expression and to block C. albicans filamentation.

Methods:
A set of five LNA-modified gapmers were designed with different chemical modifications (phosphorothioate backbone (PS) and/or palmitoyl-2’-amino-LNA) and ASO length. The in vitro performance of the different ASOs was evaluatedon their ability to control EFG1 gene expression, by qRT-PCR, and to reduce C. albicans’ filamentation, through filaments’ enumeration by microscopy. The in vivo therapeutic potential of ASOs was assessed using a G. mellonella model of infection, through a survival assay.

Results:
In vitro results showed that all ASOs were able to reduce the levels of EFG1gene expression, consequently reducing the levels of C. albicans filamentation around 50%. Interestingly, in vivo tests showed that the LNA-modified gapmer with PS backbone and palmitoyl-2’-amino-LNA was more effective at preventing G. mellonella infections.

Conclusions:
Undeniably, this work promotes the development of a novel approach for the treatment of Candida infections based on the delivery of ASOs coupled with LNA chemical modification.
FunHoMic: A Marie Skłodowska-Curie Innovative Training Network for the study of the Fungus-Host-Microbiota interplay
Authors: Cole Nathaniel , Marsaux Benoît , Rosati Diletta , Delavy Margot , Kosmala Daria , Xie Zixuan , Kaune Ann-Kristin , Valentine Marisa , Chakraborty Sayoni , Kaur Manjyot , Alaban Leovigildo Rey , Morelli Moran , Fróis-Martins Ricardo , Walker Alan , Van den Abbeele Pieter , Netea Mihai , Bougnoux Marie-Elisabeth , Manichanh Chaysavanh , Munro Carol , Hube Bernhard , Jacobsen Ilse , Roget Karine , Thomas Vincent , Queiroz Karla , Leibundgut-Landmann Salomé , Brown Alistair , d'Enfert Christophe 
Published: December 2021

Introduction
The FunHoMic project is a Marie Skłodowska-Curie Innovative Training Network comprising 13 PhD students, 8 academic partners and 3 industry partnersaimingto understand the interplay between fungi, hostsand microbiota to improve prevention and treatment of fungal infections.

Importance
About 2 billion people suffer fungal infections, which have a mortality rate close to that of malaria or breast cancer. Candida albicans has a high clinical and economic burden, making it of particular interest to the FunHoMic project. 70% of women experience at least one episode of vulvovaginal candidiasis (“thrush”) during their lifetime; 8% suffer recurring infections. C. albicans may live as a commensal but can cause symptoms when the fungus-host-microbiota equilibrium is disrupted. Infections by C. albicans have a significant clinical impact, with fatalities in severe cases. Many factors are associated with C. albicans infections; intensive care, neutropenic and diabetic patients are most at risk of systemic infection. Rising antifungal drug resistance has led to certain C. albicans infections having no treatment option.

Aim
The FunHoMic consortium combines projectson fungal pathogenesis, immunology, microbial ecology and’omics technologies to understand and exploit interactions between fungus, host and microbiota. Identification of novel bio markers on the fungal side such as genetic polymorphisms or on the host side such asmicrobiota profiles, metabolites and/or immune markers can lead to patient classification based on relative risk of infection. This could be the beginning of personalised management for fungal infections using preventive or therapeutic interventions like new antifungals, immune modulators or Live Biotherapeutic Products (LBPs).
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the MarieSklodowska-Curie grant agreement No 812969.
A glyphosate-based herbicide cross-selects for antibiotic resistance genes in bacterioplankton communities
Authors: da Costa Naíla Barbosa , Hébert Marie-Pier , Fugère Vincent , Terrat Yves , Fussmann Gregor F. , Gonzalez Andrew , Shapiro B. Jesse 
Published: December 2021

ABSTRACTAgrochemicals often contaminate freshwater bodies, affecting microbial communities that underlie aquatic food webs. For example, Roundup, a widely-used glyphosate-based herbicide (GBH), has the potential to indirectly select for antibiotic resistant bacteria. Such cross-selection could occur, for example, if the same genes (e.g. encoding efflux pumps) confer resistance to both glyphosate and antibiotics. To test for cross-resistance in natural aquatic bacterial communities, we added Roundup to 1,000-L mesocosms filled with water from a pristine lake. Over 57 days, we tracked changes in bacterial communities with shotgun metagenomic sequencing, and annotated metagenome-assembled genomes (MAGs) for the presence of known antibiotic resistance genes (ARGs), plasmids, and resistance mutations in the enzyme targeted by glyphosate (enolpyruvyl-shikimate-3-phosphate synthase; EPSPS). We found that high doses of GBH significantly increased ARG frequency and selected for multidrug efflux pumps in particular. The relative abundance of MAGs after a high dose of GBH was predictable based on the number of ARGs encoded in their genomes (17% of variation explained) and, to a lesser extent, by resistance mutations in EPSPS. Together, these results indicate that GBHs have the potential to cross-select for antibiotic resistance in natural freshwater bacteria.IMPORTANCEGlyphosate-based herbicides (GBHs) such as Roundup may have the unintended consequence of selecting for antibiotic resistance genes (ARGs), as demonstrated in previous experiments. However, the effects of GBHs on ARGs remains unknown in natural aquatic communities, which are often contaminated with pesticides from agricultural runoff. Moreover, the resistance provided by ARGs compared to canonical mutations in the glyphosate target enzyme, EPSPS, remains unclear. Here we used freshwater mesocosm experiments to show that GBHs strongly select for ARGs, particularly multidrug efflux pumps. These selective effects are evident after just a few days, and at glyphosate concentrations that are high but still within short-term (1-4 day) regulatory limits. The ability of bacteria to survive and thrive after GBH stress was predictable by the number of ARGs in their genomes, and to a lesser extent by mutations in EPSPS. GBHs are therefore likely to select for higher ARG frequencies in natural streams, lakes, and ponds.
Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis
Authors: Wilson Katherine M , Katona Eszter , Glaria Idoia , Swift Imogen J. , Sogorb-Esteve Aitana , Heller Carolin , Bouzigues Arabella , Heslegrave Amanda J , Patil Saurabh , Mohapatra Susovan , Liu Yuanjing , Goyal Jaya , Sanchez-Valle Raquel , Laforce Robert , Synofzik Matthis , Rowe James B. , Finger Elizabeth , Vandenberghe Rik , Butler Chris R. , Gerhard Alexander , van Swieten John , Seelaar Harro , Borroni Barbara , Galimberti Daniela , Mendonça Alexandre de , Masellis Mario , Tartaglia Carmela , Otto Markus , Graff Caroline , Ducharme Simon , Malaspina Andrea , Zetterberg Henrik , Boyanapalli Ramakrishna , Rohrer Jonathan D , Isaacs Adrian M 
Published: December 2021

AbstractA GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. We utilised the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the repeat expansion in CSF of people with C9orf72-associated FTD/ALS. We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intra- and inter-plate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) DPRs in the CSF of samples collected through the Genetic FTD Initiative. We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had 8-fold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.
The impact of environmental mycobiomes on geographic variation in COVID-19 mortality
Authors: Ladau Joshua , Abuabara Katrina , Walker Angelica M. , Joachimiak Marcin P. , Bansal Ishan , Wu Yulun , Hoffman Elijah B. , Kuo Chaincy , Falco Nicola , Streich Jared , van der Laan Mark J. , Wainwright Haruko M. , Brodie Eoin L. , Hess Matthias , Jacobson Daniel , Brown James B. 
Published: December 2021

AbstractMortality rates during the COVID-19 pandemic have varied by orders of magnitude across communities in the United States1. Individual, socioeconomic, and environmental factors have been linked to health outcomes of COVID-192,3,4,5. It is now widely appreciated that the environmental microbiome, composed of microbial communities associated with soil, water, atmosphere, and the built environment, impacts immune system development and susceptibility to immune-mediated disease6,7,8. The human microbiome has been linked to individual COVID-19 disease outcomes9, but there are limited data on the influence of the environmental microbiome on geographic variation in COVID-19 across populations10. To fill this knowledge gap, we used taxonomic profiles of fungal communities associated with 1,135 homes in 494 counties from across the United States in a machine learning analysis to predict COVID-19 Infection Fatality Ratios (the number of deaths caused by COVID-19 per 1000 SARS-CoV-2 infections1; ‘IFR’). Here we show that exposure to increased fungal diversity, and in particular indoor exposure to outdoor fungi, is associated with reduced SARS-CoV-2 IFR. Further, we identify seven fungal genera that are the predominant drivers of this protective signal and may play a role in suppressing COVID-19 mortality. This relationship is strongest in counties where human populations have remained stable over at least the previous decade, consistent with the importance of early-life microbial exposures11. We also assessed the explanatory power of 754 other environmental and socioeconomic factors, and found that indoor-outdoor fungal beta-diversity is amongst the strongest predictors of county-level IFR, on par with the most important known COVID-19 risk factors, including age12. We anticipate that our study will be a starting point for further integration of environmental mycobiome data with population health information, providing an important missing link in our capacity to identify vulnerable populations. Ultimately, our identification of specific genera predicted to be protective against COVID-19 mortality may point toward novel, proactive therapeutic approaches to infectious disease.
Machine learning identified distinct serum lipidomic signatures in hospitalized COVID-19-positive and COVID-19-negative patients
Authors: Castañé Helena , Iftimie Simona , Baiges-Gaya Gerard , Rodríguez-Tomàs Elisabet , Jiménez-Franco Andrea , López-Azcona Ana Felisa , Garrido Pedro , Castro Antoni , Camps Jordi , Joven Jorge 
Published: December 2021

ABSTRACTBackgroundLipids are involved in the interaction between viral infection and the host metabolic and immunological response. Several studies comparing the lipidome of COVID-19-positive hospitalized patients vs. healthy subjects have already been reported. It is largely unknown, however, whether these differences are specific to this disease. The present study compared the lipidomic signature of hospitalized COVID-19-positive patients with that of healthy subjects, and with COVID-19-negative patients hospitalized for other infectious/inflammatory diseases. Potential COVID-19 biomarkers were identified.MethodsWe analyzed the lipidomic signature of 126 COVID-19-positive patients, 45 COVID-19-negative patients hospitalized with other infectious/inflammatory diseases and 50 healthy volunteers. Results were interpreted by machine learning.ResultsWe identified acylcarnitines, lysophosphatidylethanolamines, arachidonic acid and oxylipins as the most altered species in COVID-19-positive patients compared to healthy volunteers. However, we found similar alterations in COVID-19-negative patients. By contrast, we identified lysophosphatidylcholine 22:6-sn2, phosphatidylcholine 36:1 and secondary bile acids as the parameters that had the greatest capacity to discriminate between COVID-19-positive and COVID-19-negative patients.ConclusionThis study shows that COVID-19 infection shares many lipid alterations with other infectious/inflammatory diseases, but differentiating them from the healthy population. Also, we identified some lipid species the alterations of which distinguish COVID-19-positive from Covid-19-negative patients. Our results highlight the value of integrating lipidomics with machine learning algorithms to explore the pathophysiology of COVID-19 and, consequently, improve clinical decision making.
Previous visceral leishmaniasis relapses outperform immunological or clinical signs as predictors of further relapses in patients co-infected with HIV-1
Authors: Takele Yegnasew , Mulaw Tadele , Adem Emebet , Womersley Rebecca , Kaforou Myrsini , Franssen Susanne Ursula , Levin Michael , Taylor Graham Philip , Müller Ingrid , Cotton James Anthony , Kropf Pascale 
Published: December 2021

ABSTRACTVisceral leishmaniasis (VL) and HIV co-infection (VL/HIV) has emerged as a significant public health problem in Ethiopia, with up to 30% of VL patients co-infected with HIV. These patients suffer from recurrent VL relapses and increased mortality. Our aim was to assess whether VL/HIV co-infected patients with a previous history of VL relapses (recurrent VL/HIV) have a poorer prognosis as compared to HIV patients presenting with their first episode of VL (primary VL/HIV). Our results show that recurrent VL/HIV patients have a higher parasite load, higher mortality and that their relapse-free survival is significantly shorter. The poorer prognosis of recurrent VL/HIV patients is accompanied by lower weight gain and lower recovery of all blood cell lineages, as well as lower production of IFNγ, lower CD4+ T cell counts and higher expression levels of PD1 on T cells. Furthermore, our results show that prior history of VL relapse is an important risk factor for future relapse. Both CD4+ T cell count and parasite load were also associated with a higher risk of VL relapse, but neither of these was independently associated with relapse risk after adjustment for previous VL relapse history.We propose that in addition to the current treatments, novel interventions should be considered at the time of VL diagnosis in VL/HIV patients; and suggest that improved anti-leishmanial and antiretroviral treatments, as well as immune therapy, through PD1/PDL-1 blockade and/or through IFNγ administration, could result in more efficient parasite killing and thereby reduce the relapse rate and improve survival.