bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Implementing an Infectious Diseases Approval of Selected Antimicrobials as an Antimicrobial Stewardship Initiative in a Referral Hospital in Iran
Authors: Karimzadeh Iman , Alhashemi Samira Hossaini , Ghetmiri Seyedeh Shima , Vazin Afsaneh 
Published: December 2021

Background
The excessive use of antimicrobials over the past few decades has led to an ever-increasing spread of microbial resistance, leading to increased cost and time to treat infectious diseases. The aim of this study was to investigate the clinical and economic benefits of an antimicrobial stewardship program on prescribing 5 costly used antimicrobial drugs in a large referral teaching hospital.

Methods
This study is a quasiexperimental study that focused on the consumption of the 5 costly antimicrobial drugs, including liposomal amphotericin B, caspofungin, colistimethate sodium, linezolid, and voriconazole between preintervention and postintervention plans (2016–2018). If the antimicrobial was not approved by the infectious disease physician, possible alternative medications were used. Indexes, including total consumption rate, per capita consumption, total cost, per capita cost, mortality rate, and length of hospital stay, were measured annually.

Results
There were 29,268 and 27,704 hospitalized patients that were screened primarily. Among them, 600 patients were eligible for each preintervention and postintervention phases. After the intervention, defined daily dose dropped by 18.23%, 25.51%, 9.56%, and 31.56% for amphotericin B, colistimethate sodium, caspofungin, and voriconazole, respectively. The expenditure of restricted antimicrobials decreased by 34.98% in the postimplementation of antimicrobial stewardship program (P < 0.05). The rates of hospital mortality before (40.3%) and after the intervention (38.6%) were not significantly different (P = 0.285). There is no significant result between the mean ± SD duration of hospital stays before (40.39 ± 33.07 days) and after the intervention (36.17 ± 24.84 days; P = 0.08).

Conclusions
Our study data suggest that the active contribution of infectious diseases specialist in the antimicrobial stewardship program can significantly reduce the total cost, as well as defined daily dose of high-cost antimicrobial medications along with improving the clinical outcome.
Diagnostic Dilemma and Therapeutic Challenges in Managing an Atypical Presentation of an Ocular Toxoplasmosis Patient With Myasthenia Gravis: Literature Review
Authors: Tham Zen Kuang , Lott Pooi Wah , Ee Chye Li , Ramli Norlina , Iqbal Tajunisah 
Published: December 2021

Purpose
The aim of the study was to report a case of ocular toxoplasmosis (OT) in an immunocompromised patient with myasthenia gravis, the diagnostic dilemma, and therapeutic challenges in managing the patient.

Method
This is a case report with literature review. Articles reviewed were limited to publications in English, and there were no restrictions on date, age, ethnicity, or geographic locations of patients. In addition, a brief literature review of similar reported cases was conducted to discuss about the diagnostic dilemma and therapeutic challenges in managing our patient.

Observation
We report a case of an immunocompromised, 53-year-old man who presented with rapid deterioration of left eye vision for 2 weeks. The ophthalmological examination showed nongranulomatous panuveitis with dense vitritis and retinitis with the absence of adjacent pigmented scar. Diagnostic dilemma arose as the clinical picture mimicked several possible etiologies. He was initially treated clinically as viral retinitis but failed to show improvement with antiviral treatment. Because of recent history of left empyema, he was then treated as presumed endophthalmitis and received broad-spectrum antimicrobial and antifungal therapies. He was also given oral sulfamethoxazole and trimethoprim (Bactrim) because of suspicion on OT. Despite multiple drug therapy, he still did not improve clinically. A diagnostic pars plana vitrectomy was performed and the toxoplasma polymerase chain reaction was positive. Therapeutic challenges were apparent due to limited choice of antibiotics which can be used in patients with myasthenia gravis and possible resistance to Bactrim in this case. After 6 weeks of pyrimethamine and sulfadiazine, he was clinically stable with vision of 6/60 due to macular scarring.

Conclusions
The diagnosis of atypical OT is challenging and frequently misdiagnosed as viral retinitis or endophthalmitis, leading to delayed diagnosis and treatment. Clinicians should have a high index of suspicion whenever seeing an atypical manifestation of OT in immunocompromised patients. In addition, there is very limited published data looking into the clinical presentations, diagnostic methods, treatment modalities and outcomes, specifically in reported atypical OT case reports or series. Therefore, it warrants an in-depth review to help clinician have a better understanding about this disease.
Factors Affecting Clinical Outcomes of Carbapenem-Resistant Enterobacteriaceae and Carbapenem-Susceptible Enterobacteriaceae Infections
Authors: Soontaros Suluck , Leelakanok Nattawut , Tantipong Hutsaya , Charoonwach Wacharee , Auamnoy Titinun 
Published: December 2021

Background
Carbapenem-resistant Enterobacteriaceae (CRE) is currently an emerging global public health problem and has significant negative impacts in many countries. This study aimed to identify risk factors associated with the mortality and readmission of CRE- and carbapenem-susceptible Enterobacteriaceae (CSE)–infected patients in Thailand. Length of stay (LOS) and the cost of treatment for the infections were also investigated.

Method
A retrospective cohort study was conducted in patients with CRE- and CSE-positive cultures from January 2016 to June 2019 in an advanced-level government hospital in Thailand. Risk factors for mortality and readmission were analyzed by logistic regression analysis. The differences in LOS and cost of treatment between CRE- and CSE-infected patients were analyzed by the independent t test.

Results
A total of 316 and 329 of the patients that were CRE and CSE culture positive, respectively, were included. Carbapenem-resistant Enterobacteriaceae was significantly associated with 30-day mortality [adjusted odds ratio (aOR), 2.86; 95% confidence interval (CI), 1.84–4.44; P < 0.001] and with 90-day mortality (aOR, 3.11; 95% CI, 2.01–4.83; P < 0.001). Factors that increased the risk of 30-day mortality and 90-day mortality were the Charlson Comorbidity Index score, the number of days with an invasive device or indwelling line, septic shock, acute respiratory failure, site of severe infection, and moderate to severe renal impairment. Carbapenem-resistant Enterobacteriaceae was also associated with 90-day readmission rate (aOR, 3.24; 95% CI, 1.85–5.70; P < 0.001). The LOS of CRE-infected patients and CSE-infected patients was significantly different and was 29.18 ± 36.44 and 9.78 ± 12.77 days, respectively (P < 0.001). The cost of treatment in CRE- and CSE-infected patients was significantly different (P < 0.001). The cost in CRE-infected patients was 181,183.65 ± 281,325.26 baht, whereas the cost in CSE-infected patients was 53,296.75 ± 79,316.67 baht (P < 0.001). Antibiotics for CRE-specific therapy including colistin, fosfomycin, tigecycline, or aminoglycosides, that were prescribed in combination were the mainstay treatments.

Conclusions
Carbapenem-resistant Enterobacteriaceae was an independent predictor for mortality and readmission. Length of stay and cost of treatment in CRE-infected patients were significantly higher than in CSE-infected patients.
Outcomes of SOT Recipients With COVID-19 in Different Eras of COVID-19 Therapeutics
Authors: Sait Afrah S. , Chiang Teresa Po-Yu , Marr Kieren A. , Massie Allan B. , Cochran Willa , Shah Pali , Brennan Daniel C. , Thomas Alvin G. , Mehta Steinke Seema , Permpalung Nitipong , Shoham Shmuel , Merlo Christian , Jain Tania , Boyarsky Brian , Charnaya Olga , Gurakar Ahmet , Sharma Kavita , Durand Christine M. , Werbel William A. , Huang Chiung-Yu , Ostrander Darin , Desai Niraj , Kim Min Young , Alasfar Sami , Bloch Evan M. , Tobian Aaron A.R. , Garonzik-Wang Jacqueline , Segev Dorry L. , Avery Robin K. 
Published: December 2021

Background.
Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections.

Methods.
We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March–May 2020, 21 patients; and Era 2: June–November 2020, 56 patients) and 52 solid organ transplant outpatients.

Results.
In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post–COVID-19 renal and liver function were comparable between eras, out to 90 d.

Conclusions.
Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.
Ischemic Cholangiopathy Postdonation After Circulatory Death Liver Transplantation: Donor Hepatectomy Time Matters
Authors: Goussous Naeem , Alvarez-Casas Josue , Dawany Noor , Xie Wen , Malik Saad , Gray Stephen H. , Barth Rolf N. , LaMattina John C. 
Published: December 2021

Background.
Outcomes of liver transplantation (LT) from donation after circulatory death (DCD) have been improving; however, ischemic cholangiopathy (IC) continues to be a problem. In 2014, measures to minimize donor hepatectomy time (DHT) and cold ischemic time (CIT) have been adopted to improve DCD LT outcomes.

Methods.
Retrospective review of all patients who underwent DCD LT between 2005 and 2017 was performed. We compared outcomes of patients who were transplanted before 2014 (historic group) with those who were transplanted between 2014 and 2017 (modern group).

Results.
We identified 112 patients; 44 were in the historic group and 68 in the modern group. Donors in the historic group were younger (26.5 versus 33, P = 0.007) and had a lower body mass index (26.2 versus 28.2, P = 0.007). DHT (min) and CIT (h) were significantly longer in the historic group (21.5 versus 14, P < 0.001 and 5.3 versus 4.2, P < 0.001, respectively). Fourteen patients (12.5%) developed IC, with a significantly higher incidence in the historic group (23.3% versus 6.1%, P = 0.02). There was no difference in graft and patient survival between both groups.

Conclusion.
In appropriately selected recipients, minimization of DHT and CIT may decrease the incidence of IC. These changes can potentially expand the DCD donor pool.
Altered Intercellular Communication and Extracellular Matrix Signaling as a Potential Disease Mechanism in Human Hypertrophic Cardiomyopathy
Authors: Larson Amy , Codden Christina J. , Huggins Gordon S. , Rastegar Hassan , Chen Frederick Y. , Maron Barry J. , Rowin Ethan J. , Maron Martin S. , Chin Michael T. 
Published: December 2021

AbstractObjectivesTo understand Hypertrophic Cardiomyopathy-associated alterations in gene expression and intercellular communication at the single cell level in left ventricular outflow tract lesions.BackgroundHuman hypertrophic cardiomyopathy (HCM) is considered a disorder of the sarcomere (i.e., cardiomyocytes) but the paradoxical association of nonmyocyte phenotypes such as fibrosis, mitral valve anomalies and microvascular occlusion is unexplained.MethodsTo understand the interplay between cardiomyocyte and nonmyocyte cell types in human HCM, single nuclei RNA-sequencing (snRNA-seq) was performed on myectomy specimens from HCM patients with left ventricular outflow tract obstruction and control samples from donor hearts free of cardiovascular disease.ResultsClustering analysis identified a total of 34 distinct cell populations, which were classified into 10 different cell types based on marker gene expression. Differential gene expression analysis comparing HCM to Normal datasets revealed differences in sarcomere and extracellular matrix gene expression. Analysis of expressed ligand-receptor pairs across multiple cell types indicated profound disruption in HCM intercellular communication, particularly between cardiomyocytes and fibroblasts, fibroblasts and lymphocytes and involving integrin β1 and its multiple extracellular matrix (ECM) cognate ligands.ConclusionsThese findings provide evidence for intercellular interactions in HCM that link sarcomere dysfunction with altered cardiomyocyte secretion of ECM ligands, altered fibroblast ligand-receptor interactions with a variety of cell types and increased fibroblast to lymphocyte signaling, which can further alter the ECM composition, disrupt cellular function and promote nonmyocyte phenotypes.
Prevalence of HIV and Syphilis and their Co-infection among Men Having Sex with Men in Asia: A Systematic Review and Meta-analysis
Authors: Mahmud Sultan , Mohsin Md , Muyeed Abdul , Hossain Sorif , Islam Md Mynul , Islam Ariful 
Published: December 2021

AbstractBackgroundStudies found that the group of men who have sex with men (MSM) is at a very high level of risk of HIV and sexually transmitted infections (STIs) in Asian regions due to multiple reasons. Although the prevalence of HIV among general people in Asia is considered low, the prevalence of HIV and Syphilis among MSM in this region was found very high and usually, it goes unnoticed. This study aimed to inspect the prevalence and trends of HIV, Syphilis, and their co-infection among MSM in Asia.MethodsA systematic search was performed on January 5, 2021, in PubMed, MEDLINE, and Google Scholar databases. To evaluate the heterogeneity, Q-tests and were used. To explore the publication bias, Eggers’ test and funnel plot were used. The random-effect model and subgroup analysis were performed due to the significant heterogeneity.ResultsA total of 2,872 articles were identified, and 66 articles of high quality were included in the final analysis. The overall prevalence of HIV among MSM and Syphilis was estimated considering 69 estimates from 66 studies whereas 19 estimates of co-infection were found in 17 studies. The pooled HIV prevalence was 8.48% (CI: 7.01-9.95) and the pooled Syphilis prevalence was 9.86% (CI: 8.30-11.41) with significant heterogeneity and publication bias. The pooled prevalence of HIV and Syphilis co-infection was 2.99% (CI: 1.70-4.27) with significant heterogeneity and no publication bias. The HIV, Syphilis, and HIV and Syphilis co-infection prevalence estimates exhibited an upward trend during 2002-2017.ConclusionsHIV, Syphilis, and their co-infection are quite prevalent among MSM in the Asia-Pacific region. Integrated and intensified intervention strategies, HIV testing, and improved access to antiretroviral treatment as well as increased awareness are needed to reduce HIV, Syphilis, and their co-infection among the discussed vulnerable group.
Gosha: a database of organisms with defined optimal growth temperatures
Authors: Helena-Bueno Karla , Brown Charlotte R. , Melnikov Sergey 
Published: December 2021

ABSTRACTCurrently, we are witnessing an explosive accumulation of genomic sequences for organisms across all branches of life. However, typically the genomic data lack the information about optimal growth conditions of corresponding organisms. As a result, it becomes challenging to use the genomic data for studying the adaptations of organisms and biological molecules to diverse environments. To address this problem, we have created a database Gosha, available athttp://melnikovlab.com/gshc. This database brings together information about the genomic sequences and optimal growth temperatures for 25,324 species, including ∼89% of the bacterial species with known genome sequences. Using this database, one can annotate genomic sequences from thousands of species and correlate variations in genes and genomes with optimal growth temperatures. The database interface allows users to retrieve optimal growth temperatures for bacteria, eukaryotes and archaea, providing a tool to explore how organisms, genomes, and individual proteins and nucleic acids adapt to certain temperatures. We hope that this database will contribute to medicine and biotechnology by helping to create a better understanding of molecular adaptations to heat and cold, leading to new ways to preserve biological samples, engineer useful enzymes, and develop biological materials and organisms with the desired tolerance to heat and cold.GRAPHICAL ABSTRACTGosha (available atwww.melnikovlab.com/gshc) is a database that collects information about the optimal growth temperatures of living species. This database aims to facilitate studies of molecular adaptation to specific temperatures.Abstract Figure
A quadratic analytical solution of root pressure generation provides insights about bamboo and other species
Authors: Yang Dongmei , Wang Xiaolin , Yin Mengqi , Zhang Yong-Jiang , Peng Guoquan , Tyree Melvin T. 
Published: December 2021

AbstractWe derived a steady-state model of whole root pressure generation through the combined action of all parallel segments of fine roots. This may be the first complete analytical solution for root pressure, which can be applied to complex roots/shoots.The osmotic volume of a single root is equal to that of the vessel lumen in fine roots and adjacent apoplastic spaces. Water uptake occurs via passive osmosis and active solute uptake (, osmol s−1), resulting in the osmolal concentration Cr (mol·kg−1 of water) at a fixed osmotic volume. Solute loss occurs via two passive processes: radial diffusion of solute Km(Cr-Csoil), where Km is the diffusional constant and Csoil is the soil-solute concentration) from fine roots to soil and mass flow of solute and water into the whole plant from the end of the fine roots.The proposed model predicts the quadratic function of root pressure , where b and c are the functions of plant hydraulic resistance, soil water potential, solute flux, and gravitational potential.The present study investigates the theoretical dependencies of Pr on the factors detailed above and demonstrates the root pressure-mediated distribution of water through the hydraulic architecture of a 6.8-m-tall bamboo shoot.One sentence SummaryAn analytical solution for root pressure is derived and illustrated by applying it to the measured hydraulic architecture of a 7-meter bamboo shoot.
AFP2 inhibits ABA responses during germination without ABI5 degradation but DWAs reduce desiccation tolerance
Authors: Lynch Tim , Née Guillaume , Chu Avan , Krüger Thorben , Finkemeier Iris , Finkelstein Ruth R 
Published: December 2021

AbstractOverexpression of ABI5/ABF interacting proteins (AFPs) results in extreme ABA resistance of seeds and failure to acquire desiccation tolerance, at least in part through effects on chromatin modification. This study tests the hypothesis that the AFPs promote germination by also functioning as adapters for E3 ligases that ubiquitinate ABI5, leading to its degradation. Interactions between AFPs and two well-characterized classes of E3 ligases targeting ABI5,DWD HYPERSENSITIVE TOABA (DWA)s and KEEP ON GOING (KEG), were analyzed by yeast two-hybrid, bimolecular fluorescence complementation, and genetic assays. Although the AFPs and E3 ligases showed weak direct interactions, loss of function for the E3 ligases did not impair ABA-resistance conferred by overexpression of the YFP-AFP2 fusion. Comparison of ABI5 and AFP2 levels in these lines showed that AFP2 accumulation increased during germination, but that ABI5 degradation followed germination, demonstrating that AFP2 controls ABA sensitivity during germination independently of ABI5 degradation. Surprisingly, AFP2 overexpression in thedwa1 dwa2mutant background produced the unusual combination of extreme ABA resistance and desiccation tolerance, creating an opportunity to separate the underlying biochemical characteristics of ABA sensitivity and desiccation tolerance that we investigated by quantitative proteomics. Our analysis identified at least three-fold more differentially accumulated seed proteins than previous studies. Comparison of dry seed proteomes of the different genotypes allowed us to separate and refine the changes in protein accumulation patterns correlating with desiccation tolerance independently of ABA sensitivity, orvice versa, to a subset of cold-induced and defense stress-responsive proteins and signaling regulators.Summary SentenceExtreme ABA resistance conferred by overexpression of AFP2 is not mediated by interactions with E3 ligases, but thedwabackground maintains desiccation tolerance despite ABA resistance.
Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617
Authors: Peng Lei , Hu Yingxia , Mankowski Madeleine C. , Ren Ping , Chen Rita E. , Wei Jin , Zhao Min , Li Tongqing , Tripler Therese , Ye Lupeng , Chow Ryan D. , Fang Zhenhao , Wu Chunxiang , Dong Matthew B. , Cook Matthew , Wang Guilin , Clark Paul , Nelson Bryce , Klein Daryl , Sutton Richard , Diamond Michael S. , Wilen Craig B. , Xiong Yong , Chen Sidi 
Published: December 2021

AbstractCOVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.