bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of Resistance to Nosema bombycis (Dissociodihaplophasida: Nosematidae) by Degrading NbSWP12 Using the Ubiquitin-Proteasome Pathway in Sf9-III Cells
Authors: Sun Xi , Yu Bin , Zhang Renze , Wei Junhong , Pan Guoqing , Li Chunfeng , Zhou Zeyang 
Published: October 2022

Abstract
Nosema bombycis Naegeli (Dissociodihaplophasida: Nosematidae), an obligate intracellular parasite of the silkworm Bombyx mori, causes a devastating disease called pébrine. Every year pébrine will cause huge losses to the sericulture industry worldwide. Until now, there are no effective methods to inhibit the N. bombycis infection in silkworms. In this study, we first applied both the novel protein degradation Trim-Away technology and NSlmb (F-box domain-containing in the N-terminal part of supernumerary limbs from Drosophila melanogaster) to lepidopteran Sf9-III cells to check for specific degradation of a target protein in combination with a single-chain Fv fragment (scFv). Our results showed that the Trim-Away and NSlmb systems are both amenable to Sf9-III cells. We then created transgenic cell lines that overexpressed the protein degradation system and N. bombycis chimeric scFv targeting spore wall protein NbSWP12 and evaluated the effects of the insect transgenic cell lines on the proliferation of N. bombycis. Both methods could be applied to cell lines and both Trim-Away and NSlmb ubiquitin degradation systems effectively inhibited the proliferation of N. bombycis. Further, either of these degradation systems could be applied to individual silkworms through a transgenic platform, which would yield individual silkworms with high resistance to N. bombycis, thus greatly speeding up the process of acquiring resistant strains.
Virtual Ultrasound Training in a Multinational Teaching Program
Authors: Ward Samantha , Palma James 
Published: October 2022

ABSTRACT

Introduction
Before the COVID-19 pandemic, a 1-week in-person Clinical Ultrasound Course was taught in African nations as part of a U.S. Department of State-funded program that supports and trains African peacekeepers serving with the United Nations and African Union. In order to maintain active engagement with host nations despite the travel restrictions due to the COVID-19 pandemic, portions of the course were taught virtually in 2021 to providers in Ghana, Senegal, and Rwanda. An abbreviated course was delivered covering the Focused Assessment with Sonography in Trauma (FAST) trauma exam and vascular access. The goal of this study is to assess the effectiveness of the Clinical Ultrasound Course while taught in a virtual classroom.

Materials and Methods
Thirty-six participants enrolled in the program. Participants completed a pre-course survey before the training. Training consisted of a pre-recorded lecture followed by hands-on ultrasound instruction. After the training, participants completed a post-course survey. Eight participants were excluded from the study because they did not complete both surveys. Survey questions assessed the participants’ comfort with ultrasound mechanics and the FAST exam. Participant responses were measured utilizing a visual analog scale.

Results
Based on survey results, all participants gained a better understanding of the indications and limitations of the FAST exam from the virtual Clinical Ultrasound Course. All participants also felt more comfortable using ultrasound in clinical practice than they did before the course. Ghanaian and Senegalese participants showed greater improvement in all areas studied than Rwandan participants. This is likely due to the fact that the Rwandan hospital system had prior ultrasound training and a higher baseline understanding than their counterparts. The Rwandan hospital system had previously completed the in-person sessions of the Clinical Ultrasound Course and therefore had some institutional knowledge, while the Ghanaians and Senegalese took the course for the first time during this study.

Conclusion
Virtual delivery of the Clinical Ultrasound Course was successful. Participants felt more comfortable in all aspects of ultrasound taught during the course and indicated that they were more likely to use ultrasound in clinical practice. This demonstrates that virtual ultrasound teaching is a viable option for international educational programs in the future.
Randomized Phase 3 Trial of Ruxolitinib for COVID-19–Associated Acute Respiratory Distress Syndrome*
Authors: Rein Lindsay , Calero Karel , Shah Ronak , Ojielo Charles , Hudock Kristin M. , Lodhi Saba , Sadaka Farid , Bellam Shashi , Palma Christopher , Hager David N. , Daniel Jeannie , Schaub Richard , O’Hayer Kevin , Theodoropoulos Nicole M. 
Published: October 2022

OBJECTIVES:
Evaluate the safety and efficacy of the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib in COVID-19–associated acute respiratory distress syndrome requiring mechanical ventilation.

DESIGN:
Phase 3 randomized, double-blind, placebo-controlled trial Ruxolitinib in Participants With COVID-19–Associated Acute Respiratory Distress Syndrome Who Require Mechanical Ventilation (RUXCOVID-DEVENT; NCT04377620).

SETTING:
Hospitals and community-based private or group practices in the United States (29 sites) and Russia (4 sites).

PATIENTS:
Eligible patients were greater than or equal to 12 years old, hospitalized with severe acute respiratory syndrome coronavirus 2 infection, and mechanically ventilated with a Pao
2/Fio
2 of less than or equal to 300 mm Hg within 6 hours of randomization.

INTERVENTIONS:
Patients were randomized 2:2:1 to receive twice-daily ruxolitinib 15 mg, ruxolitinib 5 mg, or placebo, each plus standard therapy.

MEASUREMENTS AND MAIN RESULTS:
The primary endpoint, 28-day mortality, was tested for each ruxolitinib group versus placebo using a mixed-effects logistic regression model and one-tailed significance test (significance threshold: p < 0.025); no type 1 error was allocated to secondary endpoints. Between May 24, 2020 and December 15, 2020, 211 patients (age range, 24–87 yr) were randomized (ruxolitinib 15/5 mg, n = 77/87; placebo, n = 47). Acute respiratory distress syndrome was categorized as severe in 27% of patients (58/211) at randomization; 90% (190/211) received concomitant steroids. Day-28 mortality was 51% (39/77; 95% CI, 39–62%) for ruxolitinib 15 mg, 53% (45/85; 95% CI, 42–64%) for ruxolitinib 5 mg, and 70% (33/47; 95% CI, 55–83%) for placebo. Neither ruxolitinib 15 mg (odds ratio, 0.46 [95% CI, 0.201–1.028]; one-sided p = 0.029) nor 5 mg (odds ratio, 0.42 [95% CI, 0.171–1.023]; one-sided p = 0.028) significantly reduced 28-day mortality versus placebo. Numerical improvements with ruxolitinib 15 mg versus placebo were observed in secondary outcomes including ventilator-, ICU-, and vasopressor-free days. Rates of overall and serious treatment-emergent adverse events were similar across treatments.

CONCLUSIONS:
The observed reduction in 28-day mortality rate between ruxolitinib and placebo in mechanically ventilated patients with COVID-19–associated acute respiratory distress syndrome was not statistically significant; however, the trial was underpowered owing to early termination.
Clinical Efficacy and Mechanism of Transcutaneous Neuromodulation on Functional Dyspepsia
Authors: Ma Yimin , Shen Jiaqing , Zhao Jing , Yang Xufeng , Yang Jun , Liu Yan , Qiao Zhenguo , Cao Youhong 
Published: October 2022

Background and Aims:
Prokinetics and proton pump inhibitors are first-line drugs for functional dyspepsia (FD) patients. However, no available treatment is effective for most FD patients, and the pathogenesis is still unclear. The purpose of this study was to investigate the therapeutic effect of transcutaneous neuromodulation (TN) on FD and its potential mechanisms.

Materials and Methods:
Fifty-seven FD patients were enrolled in the study and randomly divided into 3 groups (TN Neiguan (PC6) group, TN Zusanli (ST36) group, and sham TN group) that received corresponding treatment respectively for 4 weeks. Then, all the patients enrolled received TN PC6 combined with ST36 treatment for another 4 weeks. Dyspepsia symptom questionnaire, Medical outcomes study item short form health survey (SF-36), Hospital Anxiety and Depression Scale were used to assess the severity of symptoms. Gastric accommodation, gastric emptying rate, and related parameters of electrogastrogram were used to assess the pathophysiological mechanism of FD. The possible gastrointestinal hormonal mechanism involved was assessed by detecting serum ghrelin, neuropeptide Y, and vasoactive intestinal peptide. The possible duodenal inflammation mechanism involved was assessed by detecting duodenal mucosa.

Results:
TN treatment reduced the dyspepsia symptom score (P<0.05) and improved the quality of life. After TN treatment, the gastric accommodation (P<0.01), the gastric emptying rate (P<0.01), and the percentages of preprandial (P<0.05) and postprandial (P<0.05) gastric slow waves (GSW) were increased. The proportions of preprandial (P<0.05) and postprandial (P<0.05) gastric electrical rhythm disorder were reduced. The double acupoint combination therapy further enhanced the therapeutic effect of single acupoint. In addition, the levels of ghrelin (P<0.001) and neuropeptide Y (P<0.001) were significantly increased, the level of vasoactive intestinal peptide (P<0.001) was significantly decreased, and the total number of mast cells (P<0.001) in the duodenal bulb was significantly decreased after double acupoints combination therapy.

Conclusions:
TN treatment significantly improves the dyspepsia symptoms of FD patients and their quality of life. TN treatment increases the percentage of normal GSW, reduces the proportion of gastric electrical rhythm disorder, and improves the gastric accommodation and gastric emptying rate. The therapeutic effect of TN may be caused by regulating gastrointestinal hormone secretion and alleviating local inflammatory responses in duodenum. In addition, the improvement of TN on GSW was closely related to the decrease of bradygastria.
Utilization of hepatitis C virus-positive donors in kidney transplantation
Authors: Shetty Aneesha , Ariyamuthu Venkatesh K. , Gungor Ahmet B. , Tanriover Bekir 
Published: October 2022

Purpose of review
Direct-acting antivirals (DAA) have transformed kidney transplantation by increasing the donor pool from hepatitis C virus (HCV)-infected donors and allowing HCV nucleic acid amplification testing (NAT) donor-positive/recipient-negative (D+/R-) transplantation over the last 7 years. Willingness to accept kidneys from HCV-infected donors and timing/duration of DAA therapy have been evolving.

Recent findings
By 2021, most of the HCV NAT+ kidneys (92.6%) were transplanted to HCV-naive recipients. Despite the availability of effective DAA therapy, the discard rate of HCV NAT kidneys has been stagnant around 25%. The proportion of wait-listed patients willing to accept a deceased donor kidney from HCV Ab+ and HCV NAT+ donors increased 20-fold between 2015 and 2022. Wait-listed time to receive HCV NAT+ kidneys has been rising and most of the kidneys are transplanted to HCV-naive recipients. The proportion of deceased donor kidney transplants performed in recipients with HCV seropositivity decreased from 5.1 to 2.8% during the same period. Relatively short courses of DAA therapy (7–8 days) appear to be effective to decrease HCV transmission (<5%) and achieve sustained virological response at 12 weeks if administered prior to revascularization.

Summary
Further studies are needed to evaluate long-term outcomes of HCV NAT D+/R− transplantation and the best course of DAA treatment.
Indications for retrograde intramedullary screw fixation of the distal fibula: a retrospective cohort series
Authors: Albana Mohamed F. , Jimenez Megan L. , Brill Benjamin J. , Principe Michael J. , Quercetti Nicholas F. 
Published: October 2022

Abstract

Introduction:
Ankle fractures are a common orthopaedic injury that often require surgical fixation. Because the comorbid population in the United States continues to survive longer, it has become routine to treat comorbid patients with unstable ankle fractures. The literature has identified comorbidities known to increase the risk of ankle fracture complications to include age 55 years or older, body mass index >29.9, polytrauma, open fractures, diabetes mellitus, smoking, peripheral neuropathy, and alcohol use.

Methods:
We retrospectively reviewed 37 patients who received retrograde intramedullary screw fixation of the distal fibula, all of whom had preexisting conditions known to increase the rate of postoperative complications.

Results:
Thirty-seven patients were included in this study, of whom 36 (97.3%) went on to union. Six of 37 patients (16.2%) had complications although only one (2.7%) was due to inadequate fixation. The average time to weight-bearing as tolerated was 57.2 days (15–115 days). Two patients (5.4%) had symptomatic instrumentation requiring removal after union. Two patients (5.4%) had delayed union of the distal fibula, which responded to the use of a bone stimulator. One patient (2.7%) developed a nonunion which led to chronic subluxation of the ankle joint. One patient (2.7%) had a minor medial ankle wound complication that was treated with oral antibiotics and local wound care.

Conclusions:
Retrograde intramedullary screw fixation of the distal fibula is a viable alternative to plate and screw fixation in patients with unstable ankle fractures who have known risk factors for increased complications. However, not all distal fibula fractures are amenable to this fixation method.

Level of Evidence:
Level III retrospective cohort study.
Going Virtual: A Virtual Summer Physical Medicine and Rehabilitation Externship Experience for Medical Students
Authors: Rydberg Leslie , Ankam Nethra , Sauter Carley , Snider Brittany A. , Kasi Ravi E. , Mayer R. Samuel 
Published: October 2022

Abstract
Opportunities for early medical student exposure to the field of Physical Medicine and Rehabilitation (PM&R) are desirable for promoting the field as a career choice and are useful for introducing students to the care of people with disabilities. The COVID-19 pandemic disrupted medical education and caused the cancellation of many in person clinical programs, including the Medical Student Summer Clinical Externship (MSSCE) in PM&R supported by the Association of Academic Physiatrists (AAP). This paper describes the process by which an in-person summer clinical externship program was effectively converted into a Virtual PM&R Experience using a combination of independent assignments and small group sessions. Eighty-seven medical students completed the Virtual PM&R Experience over two summers. The participants of the program met the program learning objectives including enhancing their understanding of physiatry as a career and recognizing the medical and social issues that affect persons with disability.
Feasibility and Acceptance of a Teletrauma Surgery Consult Service to Rural and Community Hospitals: A Pilot Study
Authors: Kamine Tovy Haber , Siu Margaret , Kramer Kristina Z , Alouidor Reginald , Kelly Edward , Deutsch Ashley , Mader Timothy J , Visintainer Paul , Grochowski Kristina , Jabbour Nicolas 
Published: October 2022

BACKGROUND:
Many trauma patients currently transferred from rural and community hospitals (RCH) to Level I trauma centers (LITC) for trauma surgery evaluation may instead be appropriate for immediate discharge or admission to the local facility after evaluation by a trauma and acute care surgery (TACS) surgeon. Unnecessary use of resources occurs with current practice. We aimed to demonstrate the feasibility and acceptance of a teletrauma surgery consultation service between LITC and RCH.

STUDY DESIGN:
LITC TACS surgeons provided telehealth consults on trauma patients from 3 local RCHs. After consultation, appropriate patients were transferred to LITC; selected patients remained at or were discharged from RCH. Participating TACS surgeons and RCH physicians were surveyed.

RESULTS:
A total of 28 patients met inclusion criteria during the 5-month pilot phase, with 7 excluded due to workflow issues. The mean ± SD age was 63 ± 17 years. Of 21 patients, 7 had intracranial hemorrhage; 12 had rib fractures. The mean ± SD Injury Severity Score was 8.1 ± 4.0). A total of 6 patients were discharged from RCH, 4 admitted to RCH hospitalist service, 2 transferred to a LITC emergency room, and 9 transferred to LITC as direct admission. There was one 30-day readmission and no missed injuries or complications, or deaths. RCH providers were highly satisfied with the teletrauma surgery consultation service, TACS surgeons, and equipment used. Mental demand and effort of consulting TACS surgeons decreased significantly as the consult number increased.

CONCLUSIONS:
Teletrauma surgery consultation involving 3 RCH within our system is feasible and acceptable. A total of 10 transfers and 19 emergency department visits were avoided. There was favorable acceptance by RCH providers and TACS surgeons.
Design of Novel Selective Serotonin Reuptake Inhibitors Using Computational Modeling Studies
Authors: Svanholm Lena Elisabeth H. , Torrence Ian S. , Nguyen Tram Q. , Siegel Justin B. 
Published: October 2022

ABSTRACTLow levels of serotonin in the human brain have been associated with a variety of disorders including depression and anxiety. Selective serotonin reuptake inhibitors (SSRIs) are currently being prescribed to treat such conditions and examples of already marketed drugs include paroxetine, fluvoxamine, sertraline, and citalopram. Nevertheless, side effects such as nausea and drowsiness have been reported for these pharmaceuticals emphasizing the need for continuous development of new and improved lead molecules. In this study, chemical intuition and computational modeling were employed to propose two novel SSRI drug candidates with higher binding affinities to the ts3 human serotonin transporter (hSERT) than currently known SSRIs. Lastly, a homology analysis determined thatMacaca fascicularisis a suitable model organism for future preclinical studies.
A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions
Authors: Tang Zhongxiang , Mao Yu , Meng Yuting , Qiu Xiangjie , Bajinka Ousman , Wu Guojun , Tan Yurong 
Published: October 2022

AbstractMonkeypox has been spreading worldwide since May 2022, when the World Health Organization (WHO) declared the outbreak of a “Public health emergency of international concern”. The spread of monkeypox has posed a serious threat to the health of people all over the world but few studies have been carried out on it, and the molecular mechanism of monkeypox after infection remains unclear. We therefore implemented a transcriptome analysis to identify signaling pathways and biomarkers in monkeypox-infected cells to help understand monkeypox-host cell interactions. In this study, the dataset GSE36854 and GSE11234 were obtained from GEO. Among them, 84 significantly different genes were identified in the dataset GSE36854, followed by KEGG, GO analysis protein-protein interaction (PPI) construction and Hub gene extraction. We also analyzed the expression regulation patterns of hub genes and screened the drugs targeting the hub genes. The results showed that monkeypox-infected cells significantly activated the cellular immune response, and induced inflammatory response. IER3, IFIT2, IL11, ZC3H12A, EREG, IER2, NFKBIE, FST, IFIT1 and AREG were the top 10 hub genes, in which anti-viral gene IFIT1 and IFIT2 were significantly suppressed. AP-26113 and itraconazole promoting the expression of IFIT1 and IFIT2 may be used as new candidates for the treatment of monkeypox viral infection. Our results provide a new entry point for understanding the mode of interaction between monkeypox virus and its host.
The use of phylogenetics and ancestral sequence reconstruction to identify improved halophilic enzymes for the biodegradation of poly(R-3-hydroxybutyrate)
Authors: Quirk Stephen , Kosnicki Kassi 
Published: October 2022

AbstractEvolutionary analysis combined with ancestral sequence reconstruction (ASR) was utilized to calculate the taxonomic relationship between poly(hydroxybutyrate) depolymerase (PHBase) enzymes belonging to the halophilic genusHalomonas. Enzymes cluster into four distinct clades that differ in sequence length and composition. Like many of the previously studied PHBase proteins, there is a high degree of heterogeneity at the genus level. Ancestor sequences were calculated for each tree node using a maximum likelihood approach. The most ancestral sequence and one extant enzyme from each of the clades were expressed inEscherichia coli, purified to homogeneity, and characterized. The ancestral enzyme binds substrate more efficiently, is kinetically faster, and is more stable at elevated temperatures compared to the extant enzymes. Hence, an evolutionary phylogenetic approach is a viable alternative to other techniques for identifying optimized enzymes for industrial PHB degradation.
Substrate selectivity of the PRDM9 lysine methyltransferase domain
Authors: Hanquier Jocelyne N. , Sanders Kenidi , Berryhill Christine A. , Sahoo Firoj K. , Hudmon Andy , Vilseck Jonah Z. , Cornett Evan M. 
Published: October 2022

AbstractLysine methylation is a dynamic, post-translational mark that regulates the function of histone and non-histone proteins. Many of the enzymes that mediate lysine methylation, known as lysine methyltransferases (KMTs), were originally identified to modify histone proteins but have also been discovered to methylate non-histone proteins. In this work, we investigate the substrate selectivity of the lysine methyltransferase PRDM9 to identify both potential histone and non-histone substrates. Though normally expressed in germ cells, PRDM9 is significantly upregulated across many cancer types. The methyltransferase activity of PRDM9 is essential for double-strand break formation during meiotic recombination. PRDM9 has been reported to methylate histone H3 at lysine residues 4 and 36; however, PRDM9 KMT activity had not previously been evaluated on non-histone proteins. Using lysine-oriented peptide (K-OPL) libraries to screen potential substrates of PRDM9, we determined that PRDM9 preferentially methylates peptide sequences not found in any histone protein. We confirmed PRDM9 selectivity throughin vitroKMT reactions using peptides with substitutions at critical positions. A multisite λ-dynamics computational analysis provided a structural rationale for the observed PRDM9 selectivity. The substrate selectivity profile was then used to identify putative non-histone substrates, which were tested by peptide spot array. Finally, PRDM9 methylation non-histone substrates were validated at the protein level byin vitroKMT assays on recombinant proteins. The selectivity profile of PRDM9 will be useful in identifying putative PRDM9 substrates in different cellular contexts, and future studies are required to determine whether PRDM9 methylates non-histone proteins in the context of meiotic recombination or cancer.
Louis Pasteur and the birth of microbiology in Denmark
Authors: Høiby Niels 
Published: October 2022

Høiby N. Louis Pasteur and the birth of microbiology in Denmark. APMIS 2022. Louis Pasteur's work initiated the birth of microbiology in Denmark. Carl Julius Salomonsen was the pioneer who inspired and taught Christian Gram, Thorvald Madsen and Bernhard Bang bacteriological techniques in his annual bacteriological course which he started in 1883 at the University of Copenhagen. These pioneers developed Danish human and veterinary microbiology and became world famous. Emil Chr. Hansen developed Danish technical/industrial microbiology in the Carlsberg Laboratory and purified yeast and designed equipment for the propagation of pure yeast which was used worldwide in beer brewing. He also became world famous. The fascinating birth and development of Danish microbiology is summarized in this article, which is dedicated to the 200th birthday of Louis Pasteur, December 27, and 100th birthday of the Danish Pasteur Society, October 25, 2022.