bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell Survival Enabled by Leakage of a Labile Metabolic Intermediate
Authors: Medina-Carmona Encarnación , Gutierrez-Rus Luis I , Manssour-Triedo Fadia , Newton Matilda S , Gamiz-Arco Gloria , Mota Antonio J , Reiné Pablo , Cuerva Juan Manuel , Ortega-Muñoz Mariano , Andrés-León Eduardo , Ortega-Roldan Jose Luis , Seelig Burckhard , Ibarra-Molero Beatriz , Sanchez-Ruiz Jose M 
Published: February 2023

AbstractMany metabolites are generated in one step of a biochemical pathway and consumed in a subsequent step. Such metabolic intermediates are often reactive molecules which, if allowed to freely diffuse in the intracellular milieu, could lead to undesirable side reactions and even become toxic to the cell. Therefore, metabolic intermediates are often protected as protein-bound species and directly transferred between enzyme active sites in multi-functional enzymes, multi-enzyme complexes, and metabolons. Sequestration of reactive metabolic intermediates thus contributes to metabolic efficiency. It is not known, however, whether this evolutionary adaptation can be relaxed in response to challenges to organismal survival. Here, we report evolutionary repair experiments on Escherichia coli cells in which an enzyme crucial for the biosynthesis of proline has been deleted. The deletion makes cells unable to grow in a culture medium lacking proline. Remarkably, however, cell growth is efficiently restored by many single mutations (12 at least) in the gene of glutamine synthetase. The mutations cause the leakage to the intracellular milieu of a highly reactive phosphorylated intermediate common to the biosynthetic pathways of glutamine and proline. This intermediate is generally assumed to exist only as a protein-bound species. Nevertheless, its diffusion upon mutation-induced leakage enables a new route to proline biosynthesis. Our results support that leakage of sequestered metabolic intermediates can readily occur and contribute to organismal adaptation in some scenarios. Enhanced availability of reactive molecules may enable the generation of new biochemical pathways and the potential of mutation-induced leakage in metabolic engineering is noted.
Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients
Authors: He Yi , Jin Ying , Xue Hen , Liu Runhan , Zhang Mengyu , Liao Ruoxi , Chen Maoli , Zhou Xueli , He Xueqin , Qin Min , Li Kuo , Zou Huiqun , Gan Ying , Wang Zhenlei , Zheng Li , Zhong Hui , Fu Ping 
Published: February 2023

ABSTRACT

Background
There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF.

Methods
This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association Class II–IV HF. The concentrations of valsartan, sacubitril and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF).

Results
Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50 mg twice daily (BID), 100 mg once daily and 100 mg BID. The plasma maximum drug concentrations in the 100 mg BID group were 1995 ± 1499 ng/mL for valsartan, 171 ± 148 ng/mL for sacubitril and 13 686 ± 7418 ng/mL for LBQ657. The 24-h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25 ± 10.32 mmHg and 10.10 ± 8.00 mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00–18 198.00) from baseline, while LVEF increased by 5.00 (–0.25 to 9.25) from baseline after SV treatment.

Conclusions
PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100 mg BID SV is safe and effective in patients with PD with complications of hypertension or HF.
Programming the lifestyles of engineered bacteria for cancer therapy
Authors: Fu Shengwei , Zhang Rongrong , Gao Yanmei , Xiong Jiarui , Li Ye , Pu Lu , Xia Aiguo , Jin Fan 
Published: February 2023

ABSTRACT
Bacteria can be genetically engineered to act as therapeutic delivery vehicles in the treatment of tumors, killing cancer cells or activating the immune system. This is known as bacteria-mediated cancer therapy (BMCT). Tumor invasion, colonization and tumor regression are major biological events, which are directly associated with antitumor effects and are uncontrollable due to the influence of tumor microenvironments during the BMCT process. Here, we developed a genetic circuit for dynamically programming bacterial lifestyles (planktonic, biofilm or lysis), to precisely manipulate the process of bacterial adhesion, colonization and drug release in the BMCT process, via hierarchical modulation of the lighting power density of near-infrared (NIR) light. The deep tissue penetration of NIR offers us a modality for spatio-temporal and non-invasive control of bacterial genetic circuits in vivo. By combining computational modeling with a high-throughput characterization device, we optimized the genetic circuits in engineered bacteria to program the process of bacterial lifestyle transitions by altering the illumination scheme of NIR. Our results showed that programming intratumoral bacterial lifestyle transitions allows precise control of multiple key steps throughout the BMCT process and therapeutic efficacy can be greatly improved by controlling the localization and dosage of therapeutic agents via optimizing the illumination scheme.
Pressure-induced superconductivity at 32 K in MoB2
Authors: Pei Cuiying , Zhang Jianfeng , Wang Qi , Zhao Yi , Gao Lingling , Gong Chunsheng , Tian Shangjie , Luo Ruitao , Li Mingtao , Yang Wenge , Lu Zhong-Yi , Lei Hechang , Liu Kai , Qi Yanpeng 
Published: February 2023

ABSTRACT
Since the discovery of superconductivity in MgB2 (Tc ∼ 39 K), the search for superconductivity in related materials with similar structures or ingredients has never stopped. Although about 100 binary borides have been explored, only a few of them show superconductivity with relatively low Tc. In this work, we report the discovery of superconductivity up to 32 K, which is the highest Tc in transition-metal borides, in MoB2 under pressure. The Tc of MoB2 in the α phase can be well explained by theoretical calculations in the framework of electron-phonon coupling. Furthermore, the coupling between the d electrons of Mo and the out-of-plane Mo-phonon modes are the main driving force of the 32 K superconductivity of MoB2. Our study sheds light on the exploration of high-Tc superconductors in transition metal borides.
Androstadienone modulates human aggression in a sex-dependent manner
Authors: Wu Yin , Wei Ran , Nan Yu , Hu Yang , Ye Yuting 
Published: February 2023

AbstractChemosensory communication is ubiquitous in human social interaction. Androstadienone is a potential candidate human sex pheromone that is associated with social dominance and competition. The aim of the present study was to investigate the effects of androstadienone on aggression. We specifically distinguished two types of aggression, namely proactive and reactive aggression. Two hundred and six male and female participants received either androstadienone or a control carrier in a double-blind, placebo-controlled, between-participants design. Participants performed two aggression tasks, one on reactive aggression and the other on proactive aggression, while they were exposed to the olfactory stimuli. The results revealed that for men, smelling androstadienone reduced both reactive and proactive aggression, whereas it increased reactive aggression in women. These effects were present despite the olfactory stimuli not being explicitly discriminable. These findings provide direct evidence that androstadienone modulates human aggression in a sex-dependent manner.
Amino acid digestibility and nitrogen-corrected true metabolizable energy of mildly cooked human-grade vegan dog foods using the precision-fed cecectomized and conventional rooster assays
Authors: Roberts Leah J , Oba Patricia M , Utterback Pamela L , Parsons Carl M , Swanson Kelly S 
Published: February 2023

Abstract
The pet food market is constantly changing and adapting to meet the needs and desires of pets and their owners. One trend that has been growing in popularity lately is the feeding of fresh, human-grade foods. Human-grade pet foods contain ingredients that have all been stored, handled, processed, and transported in a manner that complies with regulations set for human food production. While most human-grade pet foods are based on animal-derived ingredients, vegan options also exist. To our knowledge, no in vivo studies have been conducted to analyze the performance of human-grade vegan diets. Therefore, the objective of this study was to investigate the amino acid (AA) digestibility and nitrogen-corrected true metabolizable energy (TMEn) of mildly cooked human-grade vegan dog foods using precision-fed cecectomized rooster and conventional rooster assays. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets (Bramble Cowbell diet (BC); Bramble roost diet (BR)), while the third was a chicken-based extruded dog diet (chicken and brown rice recipe diet (CT)). Prior to the rooster assays, both mildly cooked diets were lyophilized, and then all three diets were ground. Diets were fed to cecectomized roosters to determine AA digestibility, while conventional roosters were used to determine TMEn. All data were analyzed using the mixed models procedure of SAS (version 9.4). The majority of indispensable and dispensable AA across all diets had digestibilities higher than 80%, with a few exceptions (BC: histidine, lysine, threonine, and valine; BR: histidine). The only difference in indispensable AA digestibility among diets was observed with tryptophan, with its digestibility being higher (P = 0.0163) in CT than in BC. TMEn values were higher (P = 0.006) in BC and BR (4.55 and 4.66 kcal/g dry matter, respectively) than that in CT (3.99 kcal/g dry matter). The TMEn/GE was also higher (P = 0.0193) in BR than in CT. Metabolizable energy (ME) estimates using Atwater factors accurately estimated the energy content of CT, but modified Atwater factors and the predictive equations for ME recommended by the National Research Council underestimated energy content. All calculations underestimated the measured TMEn values of BC and BR, with Atwater factors being the closest. Although testing in dogs is required, these data suggest that mildly cooked human-grade vegan dog diets are well-digested. Moreover, TMEn data suggest that existing methods and equations underestimate the ME of the mildly cooked human-grade vegan foods tested.
Towards research-based organizational structures in mathematics tutoring centres
Authors: Byerley Cameron , Johns Carolyn , Moore-Russo Deborah , Rickard Brian , James Carolyn , Mills Melissa , Mammo Behailu , Oien Janet , Burks Linda , Heasom William , Ferreira Melissa , Farthing Cynthia , Moritz Daniel 
Published: February 2023

Abstract
Undergraduate mathematics tutoring centres are prevalent in many countries; however, there is limited research-based evidence on effective organizational structures for these centres. In this study, we consider two research questions. First, how can the quantitative and qualitative data from 10 mathematics tutoring centres be organized for research purposes? Second, what hypotheses do expert mathematics tutoring centre leaders generate about characteristics of effective centres given data from a sample of ten centres? We collected quantitative data from over 26,000 students taking mathematics courses at ten institutions. Data collected included college entrance exam scores, high school grade point average, number of student visits to the centre per eligible student and course letter grade. We used exploratory data analysis to look for relationships between visits to the tutoring centre, student grades and other variables. Qualitative centre characteristics that were considered include: specialist–generalist tutoring system, tutoring capacity, physical layout, relationships between tutors and mathematics instructors and extent of tutor training. We used the Delphi process to generate testable hypotheses from the data, such as the following: (1) The more courses a tutor is responsible for tutoring the more likely it is that the tutor will struggle to answer student questions, when the difficulty level of the courses is roughly the same. (2) Centres with more specialized tutor models have more visits per student than centres with generalized tutor models. The preceding two hypotheses, along with the other generated hypotheses, have been identified by the experts participating in this study as plausible based on professional experience, exploratory data analysis and inferences based on prior research on tutoring. This study has not rigorously shown the validity of these hypotheses; rather it lays the groundwork for future investigations to determine what combination of features characterize an effective tutoring centre.
Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic*
Authors: Anesi George L. , Andrews Adair , Bai He (Julia) , Bhatraju Pavan K. , Brett-Major David M. , Broadhurst M. Jana , Campbell Elizabeth Salvagio , Cobb J. Perren , Gonzalez Martin , Homami Sonya , Hypes Cameron D. , Irwin Amy , Kratochvil Christopher J. , Krolikowski Kelsey , Kumar Vishakha K. , Landsittel Douglas P. , Lee Richard A. , Liebler Janice M. , Lutrick Karen , Marts Lucian T. , Mosier Jarrod M. , Mukherjee Vikramjit , Postelnicu Radu , Rodina Valentina , Segal Leopoldo N. , Sevransky Jonathan E. , Spainhour Christine , Srivastava Avantika , Uyeki Timothy M. , Wurfel Mark M. , Wyles David , Evans Laura ,   for the Severe Acute Respiratory Infection-Preparedness (SARI-PREP) Study Group
Published: February 2023

OBJECTIVES:The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity.DESIGN:Prospective weekly hospital stress survey, November 2020–June 2022.SETTING:Society of Critical Care Medicine’s Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study.SUBJECTS:Thirteen hospitals across seven U.S. health systems.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82;p< 0.0001) but only moderately correlated with ED stress (ρ = 0.52;p< 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5–12%), 7% (3–10%), and 4% (2–6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9–14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6–14 wk] after local case peak;p= 0.59) while the resolution of ED stress (median 6 wk [5–6 wk] after local case peak;p= 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge.CONCLUSIONS:During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.
Aberrant fucosylation sustains the NOTCH and EGFR/NF-κB pathways and has a prognostic value in human intrahepatic cholangiocarcinoma
Authors: Ament Cindy E. , Steinmann Sara , Evert Katja , Pes Giovanni M. , Ribback Silvia , Gigante Isabella , Pizzuto Elena , Banales Jesus M. , Rodrigues Pedro M. , Olaizola Paula , Wang Haichuan , Giannelli Gianluigi , Chen Xin , Evert Matthias , Calvisi Diego F. 
Published: February 2023

Background and Aims:
Intrahepatic cholangiocarcinoma (iCCA) is a lethal malignancy, with increasing incidence worldwide and limited therapeutic options. Aberrant protein glycosylation is a hallmark of cancer. Here, we thoroughly investigated the possible involvement of fucosylation in cholangiocarcinogenesis.

Approach and Results:
We discovered that the levels of global fucosylation and members of the fucosylation pathway are ubiquitously upregulated in human iCCA tissues compared to nontumorous surrounding livers and normal biliary cells. In addition, total fucosylation levels correlate with poor patients’ prognosis. Furthermore, fucosylation inhibition following 6-alkynylfucose (6AF) administration triggered a dose-dependent decrease in the proliferation and migration of iCCA cell lines. Notably, adding fucose to the cell medium annulled these effects. At the molecular level, 6AF administration or small interfering RNA-mediated silencing of GDP-L-fucose synthetase (FX) and the GDP-fucose transmembrane transporter (SLC35C1), both pivotal players of cellular fucosylation, decreased NOTCH activity, NOTCH1/Jagged1 interaction, NOTCH receptors, and related target genes in iCCA cell lines. In the same cells, EGFR, nuclear factor kappa-light-chain-enhancer of activated B cells p65, and Bcl-xL protein levels diminished, whereas IκBα (a critical cellular NF-κB inhibitor) increased after FX/SLC35C1 knockdown or 6AF administration. In the chick chorioallantoic membrane assay, 6AF treatment profoundly suppresses the growth of iCCA cells.

Conclusions:
Elevated global fucosylation characterizes human iCCA, contributing to cell growth and migration through the upregulation of the NOTCH and EGFR/NF-κB pathways. Thus, aberrant fucosylation is a novel pathogenetic player and a potential therapeutic target for human iCCA.
MEDIUM-TERM PERFLUORO-N-OCTANE AS RESCUE POSTOPERATIVE TAMPONADE FOR VERY COMPLEX RETINAL DETACHMENTS
Authors: Shukla Dhananjay , Dhawan Anuradha , Kalliath Jay 
Published: February 2023

Purpose:
To report the anatomical and functional outcomes of medium-term perfluoro-n-octane (PFO) tamponade as a rescue procedure in very complex retinal detachments (RDs).

Methods:
We reviewed the case records of 35 consecutive patients who underwent vitrectomy for very complex RDs due to diverse etiologies. The surgical complexity was so graded because of the intraoperative failure to ascertain complete retinal reattachment; perfluoro-n-octane was used as rescue tamponade for 2 to 4 weeks. The second intervention included additional membrane peeling, retinectomy, endophotocoagulation, and gas/silicone oil tamponade. The minimum follow-up was 3 months after the final intervention: the primary outcome was retinal reattachment and the secondary outcome was change in best-corrected visual acuity (BCVA).

Results:
The most common presentations were severe trauma with retinal incarceration, preretinal and subretinal hemorrhage, or chronic/recurrent RDs with anterior proliferative vitreoretinopathy. Preoperative BCVA was ≤counting fingers in 31 (88.6%) patients. Complete retinal attachment without any tamponade was achieved in 33 (94.3%) eyes. best-corrected visual acuity improved in 30 (85.7%) eyes: 16 (45.7%) had BCVA ≥20/200 and 21 (60%) regained ambulatory vision (≥5/200). Two eyes developed keratopathy, and four needed antiglaucoma medications.

Conclusion:
We achieved excellent anatomical outcomes and acceptable functional outcomes in nearly inoperable RDs with few side effects. Medium-term perfluoro-n-octane tamponade can be used as a salvage procedure in very complex RDs where intraoperative reattachment cannot be ensured.
Incidence of Postoperative CSF Leaks in Class III Obese Patients Undergoing Middle Cranial Fossa Approach for Spontaneous CSF Leak Repair
Authors: Cutri Raffaello M. , Shibata Seiji B. , Zhang Huan , Gantz Bruce J. , Hansen Marlan R. 
Published: February 2023

Objective
To determine the safety and effectiveness of the middle cranial fossa (MCF) approach for spontaneous cerebrospinal fluid leak (sCSF-L) repair in class III obese patients. To also assess the need for prophylactic lumbar drain (LD) placement in this patient population.

Study Design
Retrospective cohort study.

Setting
Tertiary Academic Center.

Patients
All patients older than 18 years undergoing sCSF-L repair with an MCF approach.

Intervention
An MCF craniotomy for sCSF-L repair.

Main outcome measure
Rate of complications and postoperative leaks.

Results
There were no perioperative complications in 78.9% (56/71) of cases. The surgical complication rate was 12.5% (2/16), 10% (2/20), and 22.2% (6/27) in class I, class II, and class III obese patients. There was no statistically significant difference in complications among these three groups. The most common postoperative complication was a persistent CSF leak in the acute postoperative period with an overall rate of 9.9% (7/71) with six of the seven patients requiring postoperative LD placement. The percentage of postoperative CSF leaks in nonobese, class I, class II, and class III patients were 25% (2/8), 12.5% (2/16), 0% (0/20), and 11.1% (3/27), respectively. There was no statistically significant difference in the rate of postoperative CSF leaks among the four groups (chi-square, p = 0.48). In all cases, the acute postoperative CSF leaks resolved in the long term and did not require further surgical repair.

Conclusions
We determine that MCF craniotomy repair for sCSF-Ls is safe in patients with class III obesity, and the incidence of postoperative CSF leaks did not vary among other obesity classes. We also find that prophylactic placement of LDs is not routinely needed in this population.
Treatment Options in Mal de Débarquement Syndrome: A Scoping Review
Authors: Kinkhabwala Corin M. , Yuen Erick , Brennan Emily , Cadena Angel , Rizk Habib G. 
Published: February 2023

Objective
The purpose of this study was to review current treatment options available for mal de debarquement syndrome (MdDS).

Data Sources
Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines, we performed systematic search queries for MdDS-related texts. Documents must have been in the English language, and the time frame was all documents up until May 23, 2022.

Methods
Studies were selected if they were published in a peer-reviewed journal and if one of the primary objectives was the assessment of treatment for MdDS. The quality and validity of all documents were assessed by two independent co-investigators. Conflicts were resolved by a third investigator.

Results
One hundred ninety-four unique references were identified and underwent review. Ninety-seven were selected for full-text review, and 32 studies were ultimately included. Data were stratified by treatment methodology for MdDS. The categories used were pharmacologic, physical therapy, and neuromodulating stimulation.

Conclusions
Improvement in patient-reported outcomes is reported with several treatment modalities including specific protocols of vestibular rehabilitation, neuromodulating stimulation, and pharmacologic management with several types of neurotropic drugs.