bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Pharmacology and Mechanism Studies of the Protective Effect of Ginseng against Alzheimerʼs Disease Based on Aβ Pathogenesis
Authors: Liu Jinman , Yu Wenqian , Ma Cuiru , Li Tianyao , Liang Yong , Su Shijie , Zhong Guangcheng , Xie Zhouyuan , Wu Qiqing , Chen Jiaxin , Wang Qi 
Published: January 2023

AbstractAlzheimerʼs disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (Aβ) hypothesis remains the dominant one and only a few symptomatic drugs are approved for the treatment of AD. Ginseng has been widely reported as an effective herbal medicine for the treatment of neurodegenerative diseases such as dementia. Therefore, we explore the protective effects of ginseng in AD by a network pharmacological approach based on the pathogenesis of Aβ. Twenty-one major ginsenosides are screened based on ultraperformance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) data. Among them, MAPK8, MAPK9, BACE1, FLT1, CDK2, and CCR5 are the core targets. By molecular docking and validation with the in vitro cell model APPswe-SH-SY5Y, we find that ginsenosides Rg3 and Ro have good neuroprotective effects and can reduce the expression of Aβ 1 – 42 in APPswe-SH-SY5Y. Finally, through RT-qPCR experiment, we find that ginsenoside Rg3 targeted MAPK8, FLT1, and CCR5, while ginsenoside Ro targeted MAPK8, MAPK9, FLT1, and CCR5 for its potential anti-AD efficacy.
Single-Step Full-Face Surgical Treatment of the Facial Profile
Authors: Bertossi Dario , Sacchetto Luca , Chirumbolo Salvatore , Panozzo Giorgio , Kapoor Krishan Mohan 
Published: January 2023

AbstractThe present study was performed to describe how much affordable, feasible, and straightforward is the approach the authors called “single-stage full-face surgical profileplasty,” tailored to greatly improve the surgery of the facial profiling setting and achieve complete profile correction at the same time. From January 2010 to May 2019, 113 patients (95 females and 18 males; aged 19 − 63 years) were surgically treated for full-face profile amelioration. Profile correction was performed by using a combination of five procedures out of other various previously experienced: forehead fat grafting, rhinoplasty, lip fat grafting, genioplasty, and submental liposuction. All patients were assessed at 1, 3, 6, and 12 months following surgery for assessing the surgical profile treatment (SPT) outcome and any possible side effects of the combined treatment. Facial profile stability at 1 year was taken as the completion point of this treatment. Arnett et al's “Soft Tissue Cephalometric Analysis” (1999) was used to clinically evaluate the soft tissues before and after the SPT. Patients' satisfaction was measured with the Client Satisfaction Questionnaire-8” at 3 and 12 months after surgery. Statistics were used for Arnett et al's evaluation. Almost all the values were consistent and reached the normal ranges indicated by Arnett et al (p < 0.001), confirming that the desired results of the surgical profileplasty have been achieved. Single-stage full-face surgical profile treatment helps in correcting faults of the global facial deformity, in every single treated area, providing an overall improvement in facial aesthetics and harmony. Obtaining the simultaneous correction in the whole face has also the advantage of avoiding multiple surgical procedures, reducing postoperative discomfort, and the overall risks for the patient due to multiple surgical and anesthetic procedures.
Construction of Thienopyrroles through Rhodium-Catalyzed Direct Annulation of (Acetylamino)thiophenes with Alkynes
Authors: Satoh Tetsuya , Hayashi Mikishiro , Michikita Ryudai , Usuki Yoshinosuke 
Published: January 2023

AbstractThe direct annulative coupling of 3-(acetylamino)thiophenes with internal alkynes proceeds smoothly under rhodium catalysis through acetylamino-directed C–H bond cleavage at the C2-position, leading to the effective construction of 4-acetylthieno[3,2-b]pyrrole derivatives. The acetyl directing group on the annulation product is readily removed to produce the 4-unprotected thieno[3,2-b]pyrrole derivative.
Catalyst-Free Oxidation of Sulfides to Sulfoxides by gem-Dihydroperoxide under Mild Conditions
Authors: Grabovskii Stanislav A. , Andrijashina Nadezhda M. , Lobov Alexandr N. , Antipin Arkadiy V. , Safiullin Rustam L. 
Published: January 2023

AbstractA facile and efficient method for the oxidation of sulfides (dialkyl, phenylalkyl, benzylalkyl) to sulfoxides under mild conditions without using any catalysts is reported. This method afforded a series of sulfoxides with good yields (>95%). The ready accessibility and low cost of the gem-dihydroperoxides will endow it with attractive applications in chemical synthesis as oxidants.
Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators
Authors: Burke Andrew , Thomson Rachel M. , Wainwright Claire E. , Bell Scott C. 
Published: January 2023

AbstractNontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.
Associations between the Safe Prevention of Primary Cesarean Delivery Care Consensus and Maternal/Neonatal Outcomes
Authors: Estrada Pamela , Tipton Laura , Chong Rylan , Towner Dena , Yamasato Kelly 
Published: January 2023

Objective This study aimed to compare cesarean delivery (CD) rates and maternal/neonatal outcomes before and after the 2014 ACOG/SMFM Obstetric Care Consensus for Safe Prevention of Primary CD.
Study Design This retrospective study compared unscheduled CD rates and outcomes of singleton, cephalic, term pregnancies at a tertiary-care teaching maternity hospital. Births 5 years before (March 2009–February 2014) and after (June 2014–May 2019) release of the consensus were included. Chi-square and t-test were used to compare outcomes and logistic regression to adjust for confounders.
Results In this study, 44,001 pregnancies were included, 20,887 before and 23,114 after the consensus. Unscheduled CD rates increased after the consensus (12.9 vs. 14.3%, p < 0.001); however, there was no difference after adjustment (adjusted odds ratio [aOR], 0.97; 95% confidence interval [CI], 0.91–1.03). Vaginal birth after cesarean (VBAC) deliveries increased among multiparas (4.8 vs. 7.2%, p < 0.001), which remained significant after adjustment (aOR, 1.51; 95% CI, 1.37–1.66). Postpartum hemorrhage, blood transfusion, and chorioamnionitis were modestly increased, while third-degree perineal lacerations decreased. Uterine rupture and neonatal outcomes were unchanged after adjustment.
Conclusion At our tertiary-care maternity hospital, the Safe Prevention of Primary CD Care Consensus was not associated with a change in unscheduled CD, though VBAC deliveries increased. We did not demonstrate improved neonatal outcomes and showed increased maternal morbidity that warrants further study.
Key Points
Workforce Characteristics of Early Career Neonatologists and Comparison of Practice Sites
Authors: Nestander Matt , Day Colby , Lucke Ashley , Gautam Shiva , Horowitz Eric , Bernstein Sarah M. , Bhatia Anisha 
Published: January 2023

Objective Transitioning into the early career physician workforce is a uniquely challenging period in a neonatologist's career. There are limited educational opportunities in fellowship regarding career progression, practice models, and benefits. Understanding these factors are key when searching for employment. This study evaluates the early career neonatologist (ECN) workforce and employment characteristics to improve identification of professional needs.
Study Design An anonymous 59-question cross-sectional survey was distributed in July 2020 to members of the American Academy of Pediatrics Section on Neonatal Perinatal Medicine Trainees and Early Career Neonatologists (TECaN). The survey instrument was designed using SurveyMonkey and assessed search methods for identifying employers, employment contract details, and professional duties. Questions addressed clinical service time, level of acuity, protected research time, financial compensation, benefits, job search methods, and promotion requirements. Comparisons were drawn between respondents exclusively working in a university-based setting and respondents employed in nonuniversity locations. Responses were collected using SurveyMonkey and then extracted to a Microsoft Excel Workbook for analysis. Statistical analysis was performed using SAS version 9.4.
Results Of 1,302 eligible members, 348 people responded (26.7%). Forty-six percent of respondents worked in a university setting and 54% worked in a nonuniversity setting. Using employment site as a discriminator, significant differences were noted in scheduling models. University-located respondents were more likely to work 2-week block schedules, fewer weekend/weeknight call, less clinical weeks per year, and more research/administrative weeks per year. Between university and nonuniversity located positions, benefits were largely comparable, while factors perceived as influential toward promotion varied depending on practice site.
Conclusion This study provides ECNs with a contemporary workforce description vital to graduating TECaN seeking employment or renegotiating professional obligations. While benefits were largely similar based on practice site, promotion factors and scheduling models may vary depending on location.
Key Points
Preoperative Workup, Staging, and Treatment Planning of Colorectal Cancer
Authors: Abbass Mohammad Ali A. , Abbas Maher A. 
Published: January 2023

AbstractColorectal cancer (CRC) remains a leading cause of death in the United States. CRC is the second to third most common cancer globally and it impacts both genders. Screening initiatives are of paramount importance to eradicate the disease at a precancerous or early stage. Recommendations for screening are based on multiple factors including age, ethnicity, individual patient risk factors, and family history. Short- and long-term outcomes and survival data correlate with the stage of disease at the time of diagnosis emphasizing the need for appropriate baseline staging. Furthermore, stage of disease determines the necessity for any neoadjuvant or adjuvant therapy and provides recommendations for long-term oncologic follow-up. Preoperative workup includes physical examination, blood tests such as tumor markers and liver function tests, endoscopic evaluation, and cross-sectional imaging. In a select group of patients, genetic testing is part of the initial evaluation as it can impact the treatment plan, long-term follow-up, and testing of potential offspring. In general, surgical intervention remains the predominant treatment modality for stage I to III colon cancers with chemotherapy administration as adjuvant therapy for stages II to III to minimize recurrence or as a palliative modality for patients with stage IV disease. The treatment of rectal cancer remains more complex. Traditionally, early rectal cancer has been treated with surgical resection and locally advanced rectal cancer with neoadjuvant chemoradiation followed by surgical resection and postoperative chemotherapy. In the last decade, several protocols have been implemented to modify the neoadjuvant treatment with a trend toward more extended chemotherapy with the intent to further downstage the rectal cancer. Furthermore, the introduction of various protocols of total neoadjuvant chemoradiation may offer in a select group of patients with complete pathologic response, the possibility of observation without surgery. Finally, the management of stage IV CRC is in continuous evolution with the palliative goal of prolonging survival in most patients while offering the opportunity in some patients with limited metastatic disease to become potential candidates for resection of the primary lesion in addition to the metastatic disease.
Biochemical and structural characterization of a sphingomonad diarylpropane lyase for cofactorless deformylation
Authors: Kuatsjah Eugene , Zahn Michael , Chen Xiangyang , Kato Ryo , Hinchen Daniel J. , Konev Mikhail O. , Katahira Rui , Orr Christian , Wagner Armin , Zou Yike , Haugen Stefan J. , Ramirez Kelsey J. , Michener Joshua K. , Pickford Andrew R. , Kamimura Naofumi , Masai Eiji , Houk K. N. , McGeehan John E. , Beckham Gregg T. 
Published: January 2023

Lignin valorization is being intensely pursued via tandem catalytic depolymerization and biological funneling to produce single products. In many lignin depolymerization processes, aromatic dimers and oligomers linked by carbon–carbon bonds remain intact, necessitating the development of enzymes capable of cleaving these compounds to monomers. Recently, the catabolism of
erythro
-1,2-diguaiacylpropane-1,3-diol (
erythro
-DGPD), a ring-opened lignin-derived β-1 dimer, was reported in
Novosphingobium aromaticivorans
. The first enzyme in this pathway, LdpA (formerly LsdE), is a member of the nuclear transport factor 2 (NTF-2)-like structural superfamily that converts
erythro
-DGPD to lignostilbene through a heretofore unknown mechanism. In this study, we performed biochemical, structural, and mechanistic characterization of the
N. aromaticivorans
LdpA and another homolog identified in
Sphingobium
sp. SYK-6, for which activity was confirmed in vivo. For both enzymes, we first demonstrated that formaldehyde is the C
1
reaction product, and we further demonstrated that both enantiomers of
erythro
-DGPD were transformed simultaneously, suggesting that LdpA, while diastereomerically specific, lacks enantioselectivity. We also show that LdpA is subject to a severe competitive product inhibition by lignostilbene. Three-dimensional structures of LdpA were determined using X-ray crystallography, including substrate-bound complexes, revealing several residues that were shown to be catalytically essential. We used density functional theory to validate a proposed mechanism that proceeds via dehydroxylation and formation of a quinone methide intermediate that serves as an electron sink for the ensuing deformylation. Overall, this study expands the range of chemistry catalyzed by the NTF-2-like protein family to a prevalent lignin dimer through a cofactorless deformylation reaction.
Structure–function correlates of fibrinogen binding by
Acinetobacter
adhesins critical in catheter-associated urinary tract infections
Authors: Tamadonfar Kevin O. , Di Venanzio Gisela , Pinkner Jerome S. , Dodson Karen W. , Kalas Vasilios , Zimmerman Maxwell I. , Bazan Villicana Jesus , Bowman Gregory R. , Feldman Mario F. , Hultgren Scott J. 
Published: January 2023

Multidrug-resistant
Acinetobacter baumannii
infections are an urgent clinical problem and can cause difficult-to-treat nosocomial infections. During such infections, like catheter-associated urinary tract infections (CAUTI),
A. baumannii
rely on adhesive, extracellular fibers, called chaperone-usher pathway (CUP) pili for critical binding interactions. The
A. baumannii
uropathogenic strain, UPAB1, and the pan-European subclone II isolate, ACICU, use the CUP pili Abp1 and Abp2 (previously termed Cup and Prp, respectively) in tandem to establish CAUTIs, specifically to facilitate bacterial adherence and biofilm formation on the implanted catheter. Abp1 and Abp2 pili are tipped with two domain tip adhesins, Abp1D and Abp2D, respectively. We discovered that both adhesins bind fibrinogen, a critical host wound response protein that is released into the bladder upon catheterization and is subsequently deposited on the catheter. The crystal structures of the Abp1D and Abp2D receptor-binding domains were determined and revealed that they both contain a large, distally oriented pocket, which mediates binding to fibrinogen and other glycoproteins. Genetic, biochemical, and biophysical studies revealed that interactions with host proteins are governed by several critical residues in and along the edge of the binding pocket, one of which regulates the structural stability of an anterior loop motif. K34, located outside of the pocket but interacting with the anterior loop, also regulates the binding affinity of the protein. This study illuminates the mechanistic basis of the critical fibrinogen-coated catheter colonization step in
A. baumannii
CAUTI pathogenesis.
Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids
Authors: Costa Bruno , Li Calzi Marco , Castellano Mauricio , Blanco Valentina , Cuevasanta Ernesto , Litvan Irene , Ivanov Pavel , Witwer Kenneth , Cayota Alfonso , Tosar Juan Pablo 
Published: January 2023

Nonvesicular extracellular RNAs (nv-exRNAs) constitute the majority of the extracellular RNAome, but little is known about their stability, function, and potential use as disease biomarkers. Herein, we measured the stability of several naked RNAs when incubated in human serum, urine, and cerebrospinal fluid (CSF). We identified extracellularly produced tRNA-derived small RNAs (tDRs) with half-lives of several hours in CSF. Contrary to widespread assumptions, these intrinsically stable small RNAs are full-length tRNAs containing broken phosphodiester bonds (i.e., nicked tRNAs). Standard molecular biology protocols, including phenol-based RNA extraction and heat, induce the artifactual denaturation of nicked tRNAs and the consequent in vitro production of tDRs. Broken bonds are roadblocks for reverse transcriptases, preventing amplification and/or sequencing of nicked tRNAs in their native state. To solve this, we performed enzymatic repair of nicked tRNAs purified under native conditions, harnessing the intrinsic activity of phage and bacterial tRNA repair systems. Enzymatic repair regenerated an RNase R-resistant tRNA-sized band in northern blot and enabled RT-PCR amplification of full-length tRNAs. We also separated nicked tRNAs from tDRs by chromatographic methods under native conditions, identifying nicked tRNAs inside stressed cells and in vesicle-depleted human biofluids. Dissociation of nicked tRNAs produces single-stranded tDRs that can be spontaneously taken up by human epithelial cells, positioning stable nv-exRNAs as potentially relevant players in intercellular communication pathways.
On the use of there-clefts with zero subject relativizer
Authors: Kaltenböck Gunther 
Published: January 2023

Abstract
This chapter investigates the use of there-clefts without a subject relativizer (e.g. There’s a man came into the bar) in contemporary British English, a much neglected construction that is often dismissed as non-standard. Using data from the Spoken British National Corpus 2014, the study shows that it is clearly attested, with a total of 170 instances, and thus more than just a marginal syntactic anomaly. Omission of the relativizer is most frequent with the presentational-eventive type, which narrowly outnumbers the specificational type (viz. enumerative-specificational and quantifying-specificational). The relative frequency of the former is attributed to its unique pragmatic function, combining a new predication with a new referent. Structurally, this type is analysed as mono-clausal with an invariable existential prefix there’s.
Atopicality as the unmarked logical structure in Scottish Gaelic
Authors: Bartlett Tom 
Published: January 2023

Abstract
In this paper I argue that the canonical clause structure in Scottish Gaelic does not select an element as topical, but that marked structures are available to do so under specific discursive conditions. As such, Scottish Gaelic represents a previously unrecognised typological category in terms of text-organisational preferences. To make this argument I draw on discussions concerning the structure of marked atopical utterances crosslinguistically and compare these with the unmarked Gaelic structure. I draw a distinction, however, between the unmarked atopical clause in Gaelic, which I analyse as event-scoped, and the marked atopical clauses discussed in the literature, which are analysed as sentence-focused. I then demonstrate that Gaelic employs marked structures for the purposes of both topicalisation and sentence focus.
Community Engagement in Research & Policy Development: A One Health Approach to the Control of Ticks and Tick-borne Diseases in Eastern Bhutan
Authors: Namgyal Jamyang , Chedup Kinzang , Couloigner Isabelle , Cork Susan 
Published: January 2023

Summary
Livestock farming plays an important role in supporting the livelihood of resource-poor subsistence farmers in Bhutan. However, ticks and tick-borne diseases (TBDs) are major constraints on livestock farming due to their negative effect on health and production. In this case study, we illustrate how we engaged communities, academic partners from the University of Calgary (UoC), and the experts and policy makers from the Royal Government of Bhutan (RGoB) to conduct research and develop policies regarding ticks and TBDs in Bhutan. The team used a transdisciplinary approach to design and conduct an active field-surveillance programme. Live ticks were collected from cattle to determine tick species diversity, infestation prevalence and geographic distribution. Habitat suitability models were also developed for four common tick species identified in Bhutan by engaging environmental modellers from UoC. Further, we conducted face-to-face interviews with 246 farmers in eastern Bhutan to understand their knowledge, management practices and perspectives on ticks and TBDs. Five genera and 13 species of ixodid ticks were identified. Despite a high level of acaricide usage among farmers, we found that the level of knowledge about ticks and TBDs was low. The research results were shared with the communities and other stakeholders to inform and initiate the development and adoption of effective tick prevention and control measures. We conclude that such collaborative research projects using an interdisciplinary approach and involving communities have huge potential to transfer research findings into policy and practice.