bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of Drospirenone- and Ethinyl Estradiol-Related Impurities in a Combined Pharmaceutical Dosage Form by a Chromatography Method With a QbD Robustness Study
Authors: Chinta Srinivasa Reddy , Chintala Vaishnavi , Nandimalla Vishnu , Ch Rajyalakshmi , Ediga Sasikiran Goud , Kowtharapu Leela Prasad , Katari Naresh Kumar 
Published: September 2023

Abstract

Background
The estimation of drugs containing drospirenone (DRSP) and ethinyl estradiol (EE), and their related impurities, in low-dose oral contraceptive drug products is an extremely challenging target. The proposed research sought to develop and validate a stability-indicating method for quantifying drug substances and their related impurities in tablet formulation.

Objective
To develop and validate a simple, specific, accurate, precise, and stability-indicating reverse-phase (RP)-HPLC method for quantification of DRSP, EE, and their impurities in accordance with International Conference on Harmonisation (ICH) guidelines.

Method
The separation was achieved using an Agilent Zorbax SB C18 column (4.6 mm × 250 mm, 5 µm) with a detection wavelength of 215 nm and mobile phases A (100% acetonitrile) and B (acetonitrile–water, 1 + 3, v/v) at a flow rate of 1.3 mL/min and a column temperature of 40°C.

Results
The recovery study of each impurity was conducted in the range of 24 to 72 µg/mL for DRSP-related impurities and 0.2 to 0.6 µg/mL for EE-related impurities with respect to the specification limit. A linearity study was conducted over a range of 1.5 to 90 µg/mL for DRSP and DRSP-related impurities, and 0.125 to 0.75 µg/mL for EE-related impurities. A Quality by Design (QbD) study demonstrated the method’s robustness.

Conclusions
As per current guidelines, a stability-indicating method has been developed for the determination of impurities in DRSP/EE film-coated tablets. A QbD-based robustness test was performed and the method was found to be robust.

Highlights
An accurate, precise, stability-indicating, gradient RP-HPLC method has been developed and validated to determine DRSP, EE, and nine related impurities in tablet formulation. A QbD technique was used to establish a robustness study.
Generating and measuring effective vaccine-elicited HIV-specific CD8+ T cell responses
Authors: Borgo Gina M. , Rutishauser Rachel L. 
Published: September 2023

Purpose of review
There is growing consensus that eliciting CD8+ T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8+ T cells as well as major CD8+ T cell-based delivery platforms used in recent HIV vaccine clinical trials.

Recent findings
Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8+ T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8+ T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8+ T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials.

Summary
Identifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8+ T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8+ T cell-based vaccines for HIV.
Robot-assisted ileocystoplasty for the treatment of adult neurogenic bladder: A video demonstration and outcomes
Authors: Yeow Siying , Goolam Ahmed , Chung Amanda 
Published: September 2023

Abstract
Ileocystoplasty is one of the treatment options in the armamentarium for the management of adults with neurogenic bladder dysfunction, after failure of less invasive treatment alternatives, such as intravesical onabotulinum toxin A injection therapy and sacral neuromodulation. It has traditionally been performed as open surgery and can be associated with significant morbidity, especially in the early postoperative period.[1] Complications associated with open ileocystoplasty include prolonged postoperative ileus, wound infections, and pain. Performing robot-assisted ileocystoplasty can reduce the morbidity associated with open surgery[2] and has been shown to be safe and feasible in experienced hands,[3] although it may be associated with increased operative duration because of its learning curve. Our technique of robot-assisted ileocystoplasty and early postoperative outcomes is demonstrated in this video (Supplemental Digital Content, http://links.lww.com/CURRUROL/A47).
Robotic console time was 180 minutes, with minimal blood loss. Eight-hourly catheter aspiration and flushes were performed to manage the mucus in the urine. There were no metabolic acidosis or electrolyte derangements postoperatively. The patient was discharged on postoperative day 5. Postoperative cystogram at week 2 showed no leak and the patient is doing well at 1 year postoperatively. Robotic ileocystoplasty is safe and feasible and can reduce the morbidity associated with open surgery with good outcomes.
A review of transplant infectious diseases and pediatric transplant infectious diseases curriculum
Authors: Morales Megan K. , Danziger-Isakov Lara , Nematollahi Saman 
Published: September 2023

Purpose of review
As the volume and complexity of solid organ and hematopoietic stem cell transplantation continue to see rapid growth, the training of a specialized transplant infectious diseases physician workforce is of increasing interest and importance. This review provides an overview of the evolution of transplant infectious diseases training programs, essential elements of training, as well as future needs.

Recent findings
Despite the first publication of a transplant infectious diseases curriculum in 2010, more recent surveys of infectious diseases trainees have identified gaps in didactic curriculum, donor and recipient assessment, and safe living practices.

Summary
This review of transplant infectious diseases training summarizes growth through the decades, the current landscape of recommend training elements, suggested areas for continued development and expansion in training as well as novel methodologies to reach a modern trainee audience.
Papillary Hemangioma Harbors Somatic GNA11 and GNAQ Mutations
Authors: Gestrich Catherine K. , Vivero Mathew P. , Konczyk Dennis J. , Goss Jeremy A. , Labow Brian I. , Pearson Gregory D. , Cottrell Catherine E. , Mathew Mariam T. , Prasad Vinay , Kozakewich Harry P. , Fletcher Christopher D.M. , Greene Arin K. , Al-Ibraheemi Alyaa 
Published: September 2023

Papillary hemangioma (PH) is a small, primarily dermal lesion occurring predominantly in the head and neck in both children and adults. Its signature characteristics are dilated thin-walled channels containing papillary clusters of mainly capillary-sized vessels and endothelial cytoplasmic eosinophilic inclusions. Given certain histopathologic similarities to congenital hemangioma which harbor mutations in GNAQ and GNA11, we investigated whether similar mutations are present in PH. Seven PH specimens were studied. All presented in the first 4 years of life, with one being noted at birth. With the exception of one lesion, all were in the head and neck. Lesions were bluish and ranged in size from 0.5 to 2.8 cm. Four samples had GNA11 p.Q209L and 3 had GNAQ p.Q209L missense mutations. Mutations in GNA11 and GNAQ are associated with other types of somatic vascular lesions including capillary malformation, congenital hemangioma, anastomosing hemangioma, thrombotic anastomosing hemangioma, and hepatic small cell neoplasm. Shared mutations in GNA11 and GNAQ may account for some overlapping clinical and pathologic features in these entities, perhaps explicable by the timing of the mutation or influence of the germline phenotype.
Evaluating Potential Disparities in Geospatial Access to ACS/AAST Verified Emergency General Surgery Centers
Authors: Silver David S. , Beiringer Jamison , Lu Liling , Peitzman Andrew B. , Neal Matthew D. , Brown Joshua B. 
Published: September 2023

ABSTRACT

Background
The American Association for the Surgery of Trauma and the American College of Surgeons have recently introduced emergency general surgery (EGS) center verification, which could enhance patient outcomes. Distance and resource availability may affect access to these centers, which has been linked to higher mortality. Although many patients can receive adequate care at community centers, those with critical conditions may require specialized treatment at EGS-verified centers. We aimed to evaluate geospatial access to potential EGS-verified centers and identify disparities across different scenarios of EGS verification program uptake in the US.

Methods
We utilized hospital capabilities and verified pilot centers to estimate potential patterns of which centers would become EGS verified under four scenarios (EGS centers; high volume EGS centers; high volume EGS + level 1 trauma centers; quaternary referral centers). We calculated the spatial accessibility index (SPAI) using an enhanced 2-step floating catchment technique to determine geospatial access for each scenario. We also evaluated social determinants of health across geospatial access using the Area Deprivation Index (ADI).

Results
1932 hospitals were categorized as EGS centers, 307 as high volume EGS centers, 401 as high volume EGS + level 1trauma centers; and 146 as quaternary centers. SPAI decreased as the stringency of EGS verification increased in each scenario (226.6 [111.7, 330.7]; 51.8 [0, 126.1]; 71.52 [3.34-164.56]; 6.2 [0, 62.2], p < 0.001). Within each scenario, SPAI also declined as the ADI quartile increased (p < 0.001). The high volume EGS + level 1trauma center scenario had the most significant disparity in access between the 1st and 4th ADI quartiles (-54.68).

Conclusions
Access to EGS-verified centers may vary considerably based on the program's implementation. Disadvantaged communities may be disproportionately affected by limited access. Further work to study regional needs can allow a strategic implementation of the EGS verification program to optimize outcomes while minimizing disparities.

Evidence Level
Level III, Epidemiological
Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference
Authors: Chadha Ryan , Sakai Tetsuro , Rajakumar Akila , Shingina Alexandra , Yoon Uzung , Patel Dhupal , Spiro Michael , Bhangui Pooja , Sun Li-Ying , Humar Abhinav , Bezinover Dmitri , Findlay James , Saigal Sanjiv , Singh Shweta , Yi Nam-Joon , Rodriguez-Davalos Manuel , Kumar Lakshmi , Kumaran Vinay , Agarwal Shaleen , Berlakovich Gabriela , Egawa Hiroto , Lerut Jan , Clemens Broering Dieter , Berenguer Marina , Cattral Mark , Clavien Pierre-Alain , Chen Chao-Long , Shah Samir , Zhu Zhi-Jun , Ascher Nancy , Bhangui Prashant , Rammohan Ashwin , Emond Jean , Rela Mohamed 
Published: September 2023

Background.
During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS).

Methods.
A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India.

Results.
It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion.

Conclusions.
Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.
Rescue Liver Transplantation for Posthepatectomy Liver Failure: A Systematic Review and Survey of an International Experience
Authors: Azoulay Daniel , Desterke Christophe , Bhangui Prashant , Serrablo Alejandro , De Martin Eleonora , Cauchy François , Salloum Chady , Allard Marc Antoine , Golse Nicolas , Vibert Eric , Sa Cunha Antonio , Cherqui Daniel , Adam René , Saliba Faouzi , Ichai Philippe , Feray Cyrille , Scatton Olivier , Lim Chetana 
Published: September 2023

Background.
Rescue liver transplantation (LT) is the only life-saving option for posthepatectomy liver failure (PHLF) whenever it is deemed as irreversible and likely to be fatal. The goals were to perform a qualitative systematic review of rescue LT for PHLF and a survey among various international LT experts.

Methods.
A literature search was performed from 2000 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Population, Intervention, Comparison, Outcome framework, and to this, the authors’ experience was added. The international online open survey included 6 cases of PHLF extracted from the literature and submitted to 976 LT experts. The primary outcome was whether experts would consider rescue LT for each case. Interrater agreement among experts was calculated using the free-marginal multirater kappa methodology.

Results.
The review included 40 patients. Post-LT mortality occurred in 8 (20%) cases (7/28 with proven cancer and 1/12 with benign disease). In the long term, 6 of 21 (28.6%) survivors with cancer died of recurrence (median = 38 mo) and 15 (71.4%) were alive with no recurrence (median = 111 mo). All 11 survivors with benign disease were alive and well (median = 39 mo). In the international survey among experts in LT, the percentage agreement to consider rescue LT was 28%–98%, higher for benign than for malignant disease (P = 0.011). Interrater agreement for the primary endpoint was low, expected 5-y survival >50% being the strongest independent predictor to consider LT.

Conclusions.
Rescue LT for PHLF may achieve good results in selected patients. Considerable inconsistencies of decision-making exist among LT experts when considering LT for PHLF.
Falsirhodobacter algicola sp. nov., a member of the Rhodobacteraceae isolated from the marine red algae Grateloupia sp.
Authors: Cho Eun-Seo , An Chang Woo , Bae Seung Seob , Chung Dawoon , Yu Woon-Jong , Kim Jaoon Young Hwan , Choi Grace , Kwon Yong Min 
Published: September 2023

A Gram-negative, pale yellow-pigmented, non-flagellated, motile, rod-shaped and aerobic bacterium, designated strain PG104T, was isolated from red algae Grateloupia sp. collected from the coastal area of Pohang, Republic of Korea. Growth of strain PG104T was observed at 15–35 °C (optimum, 30 °C), pH 6.0–10.0 (optimum, pH 7.5–8.0) and in the presence of 0–8.0 % (w/v) NaCl (optimum, 5.0 %). The predominant fatty acids included C17 : 0, C18 : 0, 11-methyl C18 : 1
ω7c and summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and the major respiratory quinone was Q-10. Polar lipids included phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified lipid and one unidentified aminolipid. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain PG104T formed a phylogenetic lineage with members of the genus

Falsirhodobacter

and exhibited 16S rRNA gene sequence similarities of 97.1 and 96.6 % to

Falsirhodobacter deserti

W402T and

Falsirhodobacter halotolerans

JA744T, respectively. The complete genome of strain PG104T consisted of a single circular chromosome of approximately 2.8 Mbp with five plasmids. Based on polyphasic taxonomic data, strain PG104T represents a novel species in the genus

Falsirhodobacter

, for which the name Falsirhodobacter algicola sp. nov. is proposed. The type strain of Falsirhodobacter algicola is PG104T (=KCTC 82230T=JCM 34380T).
The effect of single mutations in Zika virus envelope on escape from broadly neutralizing antibodies
Authors: Kikawa Caroline , Cartwright-Acar Catiana H. , Stuart Jackson B. , Contreras Maya , Levoir Lisa M. , Evans Matthew J. , Bloom Jesse D. , Goo Leslie 
Published: September 2023

AbstractZika virus and dengue virus are co-circulating flaviviruses with a widespread endemic range. Eliciting broad and potent neutralizing antibodies is an attractive goal for developing a vaccine to simultaneously protect against these viruses. However, the capacity of viral mutations to confer escape from broadly neutralizing antibodies remains undescribed, due in part to limited throughput and scope of traditional approaches. Here, we use deep mutational scanning to map how all possible single amino acid mutations in Zika virus envelope protein affect neutralization by antibodies of varying breadth and potency. While all antibodies selected viral escape mutations, the mutations selected by broadly neutralizing antibodies conferred less escape relative to those selected by narrow, virus-specific antibodies. Surprisingly, even for broadly neutralizing antibodies with similar binding footprints, different single mutations led to escape, indicating distinct functional requirements for neutralization not captured by existing structures. Additionally, the antigenic effects of mutations selected by broadly neutralizing antibodies were conserved across divergent, albeit related, flaviviruses. Our approach identifies residues critical for antibody neutralization, thus comprehensively defining the as-yet-unknown functional epitopes of antibodies with clinical potential.ImportanceThe wide endemic range of mosquito-vectored flaviviruses – such as Zika virus and dengue virus serotypes 1-4 – places hundreds of millions of people at risk of infection every year. Despite this, there are no widely available vaccines, and treatment of severe cases is limited to supportive care. An avenue towards development of more widely applicable vaccines and targeted therapies is the characterization of monoclonal antibodies that broadly neutralize all these viruses. Here, we measure how single amino acid mutations in viral envelope protein affect neutralizing antibodies with both broad and narrow specificities. We find that broadly neutralizing antibodies with potential as vaccine prototypes or biological therapeutics are quantifiably more difficult to escape than narrow, virus-specific neutralizing antibodies.
A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system
Authors: Costacurta Francesco , Dodaro Andrea , Bante David , Schöppe Helge , Sprenger Bernhard , Moghadasi Seyed Arad , Fleischmann Jakob , Pavan Matteo , Bassani Davide , Menin Silvia , Rauch Stefanie , Krismer Laura , Sauerwein Anna , Heberle Anne , Rabensteiner Toni , Ho Joses , Harris Reuben S. , Stefan Eduard , Schneider Rainer , Kaserer Teresa , Moro Stefano , von Laer Dorothee , Heilmann Emmanuel 
Published: September 2023

AbstractNirmatrelvir was the first protease inhibitor (PI) specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mproresistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mprovariants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available PIs (nirmatrelvir and ensitrelvir) with cell-based and biochemical assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mproinhibitors, will help to understand SARS-CoV-2 protease-inhibitor-resistance mechanisms and show the relevance of specific mutations in the clinic, thereby informing treatment decisions.TeaserUnderstanding how SARS-CoV-2 could counter the antiviral drug nirmatrelvir and what it means for the future of COVID-19 treatment.
Resuscitating Sleeping Beauties: reviving a six-hundred-year-old amoeba and endosymbiont
Authors: Issam Hasni , Tall Mamadou Lamine , Bailly Matthieu Le , Colson Philippe , Levasseur Anthony , Raoult Didier , Scola Bernard La , Drancourt Michel 
Published: September 2023

ABSTRACTCoprolites are sources of ancient human gut microbiota and parasites. Paleomicrobiological investigation of a 14th-century coprolite revealed amoeba cysts that when cultured were identified asAcanthamoeba castellaniistrain Namur. Genomic DNA sequencing indicated a 69-Mb, 57.9% GC content genome encoding 40,545 proteins, including 266 amoeba sequences sharing the best hit with amoeba-resisting microorganisms, including 170 with giant viruses. An endosymbiont we namedCoprolita marseillensiswas revealed by electron microscopy that harbored a 1-Mb genome of Rickettsiales ancestry encoding 1,738 predicted genes. Most of the amoeba genomic complement was related to biological functions giving the amoeba the capacity to survive in various ecological niches, including genes associated with anaerobic respiration and dormancy that were detected in bacteria resuscitated from permafrost, but not in controls that had not been resurrected. Investigating these 600-year-old “sleeping beauties” indicated the centuries-long survival of unicellular organisms and the mixed capability of anaerobic respiration coupled with dormancy.