bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel medication safety training module
Authors: Kasal Taylor , Sabol Kyle
Published: June 2022

Purpose

Escape rooms are effective educational tools for engaging learners and may serve as a strategy for medication safety training to increase perceived learned safety measures and knowledge retention. Escape rooms are lifelike environments in which participants work together to solve a succession of puzzles to escape a locked room in the allotted time. Novel medication safety training modules such as a pharmacy escape room allow medical errors to be simulated in a team-based, controlled environment focusing on system improvement to establish a culture of safety. This project was conducted to improve medication safety knowledge using a novel pharmacy escape room training module piloted within a large, integrated pharmacy department.

Several pilot groups of 2 or more pharmacy employees took part in a virtual medication safety escape room as part of a training module at Advocate Aurora Health between January and March 2021. Participants included pharmacists and pharmacy technicians employed at Aurora St. Luke’s Medical Center, Aurora Sinai Medical Center, and Pharmacy Integrated Clinical Services. Assessments were administered before and after completion of the escape room module to evaluate medication safety knowledge and perceived learned safety measures by comparing scores. A total of 101 employees participated in the pharmacy escape room, with an average escape time of 42 minutes. Overall assessment scores before completion of the escape room module ranged from 20% to 86.6%, while those afterwards ranged from 33.3% to 93.3%. Participant feedback was positive, with reports that the novel escape room training module was more engaging and interactive than the alternative online self-paced learning modules.

Conclusion

Virtual escape rooms can be used as a novel medication safety training module to increase medication safety knowledge and allow medical errors to be simulated in a controlled environment. Incorporating high-reliability tools and tactics into development of the escape room can promote safe medication practices and reinforce principles of high-reliability organizations.
Multi-omics to characterize the functional relationships of R-loops with epigenetic modifications, RNAPII transcription and gene expression
Authors: Pan Xingxin , Huang L Frank
Published: June 2022

Abnormal accumulation of R-loops results in replication stress, genome instability, chromatin alterations and gene silencing. Little research has been done to characterize functional relationships among R-loops, histone marks, RNA polymerase II (RNAPII) transcription and gene regulation. We built extremely randomized trees (ETs) models to predict the genome-wide R-loops using RNAPII and multiple histone modifications chromatin immunoprecipitation (ChIP)-seq, DNase-seq, Global Run-On sequencing (GRO-seq) and R-loop profiling data. We compared the performance of ET models to multiple machine learning approaches, and the proposed ET models achieved the best and extremely robust performances. Epigenetic profiles are highly predictive of R-loops genome-widely and they are strongly associated with R-loop formation. In addition, the presence of R-loops is significantly correlated with RNAPII transcription activity, H3K4me3 and open chromatin around the transcription start site, and H3K9me1 and H3K9me3 around the transcription termination site. RNAPII pausing defects were correlated with 5′R-loops accumulation, and transcriptional termination defects and read-throughs were correlated with 3′R-loops accumulation. Furthermore, we found driver genes with 5′R-loops and RNAPII pausing defects express significantly higher and genes with 3′R-loops and read-through transcription express significantly lower than genes without R-loops. These driver genes are enriched with chromosomal instability, Hippo–Merlin signaling Dysregulation, DNA damage response and TGF-β pathways, indicating R-loops accumulating at the 5′ end of genes play oncogenic roles, whereas at the 3′ end of genes play tumor-suppressive roles in tumorigenesis.
The presynaptic active zone protein Bassoon as a marker for synapses between Type III cells and afferent nerve fibers in taste buds
Authors: Ikuta Rio , Hamada Shun
Published: June 2022

Taste buds are receptor organs for gustation. Two types of taste receptor cells have been identified in taste buds: Type II and Type III cells. Type III cells connect with afferent fibers through conventional chemical synapses. In the present study, we used immunocytochemistry to examine the distribution pattern of Bassoon, a scaffolding protein of the cytomatrix at the active zones of conventional synapses in mouse taste buds. Bassoon was predominantly detected as small puncta in Type III cells. Bassoon-immunoreactive puncta were observed in proximity to or partially overlapping with intragemmal nerve fibers. The distribution pattern of Bassoon in taste buds was similar among circumvallate, fungiform, and foliate taste buds. Immunoelectron microscopy showed Bassoon at the active zones of the conventional synapses of Type III cells in circumvallate taste buds. The present results demonstrate that Bassoon is a marker for synapses between Type III cells and afferent fibers in mouse taste buds.
Early Treatment of High-Risk Hospitalized Coronavirus Disease 2019 (COVID-19) Patients With a Combination of Interferon Beta-1b and Remdesivir: A Phase 2 Open-label Randomized Controlled Trial
Authors: Tam Anthony Raymond , Zhang Ricky Ruiqi , Lung Kwok-Cheung , Liu Raymond , Leung Ka-Yi , Liu Danlei , Fan Yujing , Lu Lu , Lam Athene Hoi-Ying , Chung Tom Wai-Hin , Yip Cyril Chik-Yan , Lo Jenny , Wu Alan Ka-Lun , Lee Rodney , Sin Simon , Ng Pauline Yeung , Chan Wai-Ming , Shum Hoi-Ping , Yan Wing-Wa , Chan Jasper Fuk-Woo , Cheng Vincent Chi-Chung , Lau Chak-Sing , To Kelvin Kai-Wang , Chan Kwok-Hung , Yuen Kwok-Yung , Hung Ivan Fan-Ngai
Published: June 2022

Background

Early antiviral therapy was effective in the treatment of coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients.

Methods

We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200 mg loading on day 1 followed by 100 mg daily on day 2 to 5 (combination group), or to remdesivir only of similar regimen (control group) (1:1). The primary endpoint was the time to complete alleviation of symptoms (NEWS2 = 0).

Results

Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom onset was 3 days. The median age was 65 years, and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary endpoint, the combination group was significantly quicker to NEWS2 = 0 (4 vs 6.5 days; hazard ratio [HR], 6.59; 95% confidence interval [CI], 6.1–7.09; P < .0001) when compared to the control group. For the secondary endpoints, the combination group was quicker to negative nasopharyngeal swab (NPS) viral load (VL) (6 vs 8 days; HR, 8.16; 95% CI, 7.79–8.52; P < .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P < .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P < .0001) was the most significant independent factor associated with NEWS2 = 0 on day 4.

Conclusions

Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, and in shortening viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.

Clinical Trials Registration

NCT04647695.
Vaccine Coverage Associated With Ending a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Wave: A Retrospective Longitudinal Analysis
Authors: Glatman-Freedman Aharona , Feldman Sarah F , Hershkovitz Yael , Kaufman Zalman , Dichtiar Rita , Keinan-Boker Lital , Bromberg Michal
Published: June 2022

Background

Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021.

Methods

The daily percentage of new polymerase chain reaction (PCR)–confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV).

Results

A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees.

Conclusions

The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.
Population Genomic Time Series Data of a Natural Population Suggests Adaptive Tracking of Fluctuating Environmental Changes
Authors: Pfenninger Markus , Foucault Quentin
Published: June 2022

Natural populations are constantly exposed to fluctuating environmental changes that negatively affect their fitness in unpredictable ways. While theoretical models show the possibility of counteracting these environmental changes through rapid evolutionary adaptations, there have been few empirical studies demonstrating such adaptive tracking in natural populations.

Here, we analyzed environmental data, fitness-related phenotyping and genomic time-series data sampled over 3 years from a natural Chironomus riparius (Diptera, Insecta) population to address this question. We show that the population's environment varied significantly on the time scale of the sampling in many selectively relevant dimensions, independently of each other. Similarly, phenotypic fitness components evolved significantly on the same temporal scale (mean 0.32 Haldanes), likewise independent from each other. The allele frequencies of 367,446 SNPs across the genome showed evidence of positive selection. Using temporal correlation of spatially coherent allele frequency changes revealed 35,574 haplotypes with more than one selected SNP. The mean selection coefficient for these haplotypes was 0.30 (s.d. = 0.68). The frequency changes of these haplotypes clustered in 46 different temporal patterns, indicating concerted, independent evolution of many polygenic traits. Nine of these patterns were strongly correlated with measured environmental variables. Enrichment analysis of affected genes suggested the implication of a wide variety of biological processes.

Thus, our results suggest overall that the natural population of C. riparius tracks environmental change through rapid polygenic adaptation in many independent dimensions. This is further evidence that natural selection is pervasive at the genomic level and that evolutionary and ecological time scales may not differ at all, at least in some organisms.
Population-Level Correlation Between Incidence of Curable Sexually Transmitted Infections and Human Immunodeficiency Virus (HIV)-1 Among African Women Participating in HIV-1 Pre-Exposure Prophylaxis Trials
Authors: Hunidzarira Portia , Brown Elizabeth R , Chirenje Z Mike , Hillier Sharon L , Marrazzo Jeanne M , Palanee-Phillips Thesla , Kiweewa Flavia M , Baeten Jared M ,   for the MTN-003/VOICE and MTN-020/ASPIRE Study Teams
Published: June 2022

Background

Highly efficacious oral pre-exposure prophylaxis (PrEP) is the global standard for human immunodeficiency virus (HIV)-1 prevention, including in clinical trials of novel PrEP agents using active-comparator designs. The analysis assessed whether incident sexually transmitted infections (STIs) can serve as a surrogate indicator of HIV-1 incidence that might occur in the absence of PrEP.

Methods

We analyzed data from 3256 women randomized to placebo groups of oral and vaginal PrEP trials (MTN-003/VOICE and MTN-020/ASPIRE). Regression modeling assessed the correlation between incident individual STIs (Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, each considered separately) and incident HIV-1.

Results

Across 18 sites in 4 countries (Malawi, South Africa, Uganda, Zimbabwe), STI and HIV-1 incidences were high: HIV-1 4.9, N gonorrhoeae 5.3, C trachomatis 14.5, and T vaginalis 7.1 per 100 person-years. There was limited correlation between HIV-1 incidence and incidence of individual STIs: N gonorrhoeae (r = 0.02, P = .871), C trachomatis (r = 0.49, P = <.001), and T vaginalis (r = 0.10, P = .481). The modest association with C trachomatis was driven by country-level differences in both C trachomatis and HIV-1, with no statistically significant association within countries.

Conclusions

Sexually transmitted infection incidence did not reliably predict HIV-1 incidence at the population level among at-risk African women participating in 2 large PrEP trials.
Moenomycin is broadly active against multidrug-resistant Neisseria gonorrhoeae and clears an infection from a murine vaginal tract infection model
Authors: Yang Fan , Gao Shuai , Yan Jing , Lin Xu’ai , van der Veen Stijn
Published: June 2022

Objectives

Ceftriaxone therapy for gonorrhoea has become under increasing pressure due to waning susceptibility levels and emergence of high-level resistant strains such as the FC428 clone. Moenomycin was recently identified to display potent anti-gonococcal activity against some reference strains. Therefore, the aim of this study was to investigate moenomycin in vitro and in vivo antimicrobial activity.

Methods

Moenomycin in vitro antimicrobial activity was investigated against 575 clinical isolates, including strains associated with the FC428 clone, using the agar dilution method. Moenomycin in vivo activity was investigated in a mouse vaginal tract gonococcal infection model.

Results

The moenomycin MIC range for the strain collection was 0.004–0.06 mg/L, with a MIC50 of 0.016 mg/L and a MIC90 of 0.03 mg/L. The correlation between moenomycin and ceftriaxone susceptibility levels was poor (R = 0.13), while the fractional inhibitory concentration index (FICI) resulted in indifference for all tested strains. Therefore, development of cross-resistance between moenomycin and ceftriaxone is unlikely for N. gonorrhoeae. Determination of the moenomycin mode of activity against N. gonorrhoeae by time–kill assays showed that moenomycin is bactericidal, with over 104-fold inactivation observed after 4 h exposure. Finally, an intramuscular moenomycin dose of 10 mg/kg given on 2 consecutive days was able to clear a gonococcal infection in a mouse vaginal tract infection model within 1–3 days after the second dose, which was significantly faster than for mice treated with the vehicle control (P < 0.0001).

Conclusions

Moenomycin displays potent in vitro and in vivo antimicrobial activity against N. gonorrhoeae, warranting further exploration as alternative therapy.
Once-daily dolutegravir versus darunavir plus cobicistat in adults at the time of primary HIV-1 infection: the OPTIPRIM2-ANRS 169 randomized, open-label, Phase 3 trial
Authors: Chéret Antoine , Bauer Rebecca , Meiffrédy Vincent , Lopez Pauline , Ajana Faïza , Lacombe Karine , Morlat Philippe , Lascoux Caroline , Reynes Jacques , Calin Ruxandra , Abel Sylvie , Goujard Cécile , Rouzioux Christine , Avettand-Fenoel Véronique , Meyer Laurence
Published: June 2022

Background

Whether integrase strand transfer inhibitors (INSTIs) can decrease HIV-1 DNA levels more rapidly than boosted PIs during primary HIV-1 infection (PHI) is unknown. We hypothesized that once-daily dolutegravir/tenofovir/emtricitabine could reduce the viral reservoir through rapid viral replication control further than once-daily darunavir/cobicistat/tenofovir/emtricitabine.

Methods

The OPTIPRIM2-ANRS 169 study was a randomized (1:1), open-label, multicentre trial in adults with ≤5 or ≤3 HIV antibodies detected, respectively, by western blot or immunoblot in the last 10 days. The primary endpoint was total HIV-1 DNA levels in PBMCs at Week 48 (W48) adjusted for baseline levels. The main secondary endpoint was HIV-1 RNA level decrease.

Results

Between April 2017 and August 2018, 101 patients were included from 31 hospitals. Most patients were men (93%), the median age was 36 years and 17% were Fiebig stage ≤3. The median (IQR) plasma HIV-1 RNA and DNA levels were, respectively, 5.8 (5.0–6.6) and 3.87 (3.52–4.15) log10 copies/million PBMCs. The median (IQR) decreases in HIV-1 DNA levels at W48 were −1.48 (−1.74 to −1.06) and −1.39 (−1.55 to −0.98) log10 copies/million PBMCs in the dolutegravir and darunavir/cobicistat groups, respectively (P = 0.52). Plasma HIV-1 RNA levels were <50 copies/mL in 24% versus 0% of patients in the dolutegravir and darunavir/cobicistat groups at W4, 55% versus 2% at W8, 67% versus 17% at W12, and 94% versus 90% at W48, respectively.

Conclusions

Dolutegravir-based and darunavir-based regimens initiated during PHI strongly and similarly decreased the blood reservoir size. Considering the rapid viral suppression during a period of high HIV-1 transmission risk, dolutegravir-based regimens are a major first-line option.
Attraction and Longevity of 2- and 3-Component Food Cone Lures for the Caribbean Fruit Fly, Anastrepha suspensa (Diptera: Tephritidae)
Authors: Vázquez Aimé , Cloonan Kevin R , Rohde Barukh B , Gill Micah A , Mosser Lisa K , Crane Jonathan H , Carrillo Daniel , Kendra Paul E
Published: June 2022

The Caribbean fruit fly, Anastrepha suspensa (Loew) (Diptera: Tephritidae), is a quarantine pest of Citrus spp. and a production pest of guava and other specialty fruits in Florida. Effective monitoring lures and traps are needed for early pest detection and timely initiation of control measures. As part of a continued effort to identify attractive synthetic lures for the Caribbean fruit fly, we conducted field tests in Homestead, Florida to compare the efficacy and longevity of commercial 2- and 3-component cone lures (2C [ammonium acetate and putrescine], 3C [ammonium acetate, putrescine, and trimethylamine]), the current standards used by regulatory agencies, versus the traditional liquid protein bait consisting of hydrolyzed torula yeast and borax as a positive control. Additional lures were also field-aged and periodically brought into the laboratory to quantify residual chemical contents. Traps baited with the torula yeast-borax mixture captured the highest mean number of A. suspensa, and traps baited with the commercial 2C lures captured more flies than the 3C lures. Traps baited with torula yeast-borax also captured the highest number of nontarget Diptera. Captures with all three treatments were significantly biased toward females. Attractiveness of the 2C lure began to drop after 6–8 wk, and the 3C lure after 5–6 wk. Overall, these data suggest that the 2C cone lure is more attractive to A. suspensa than the 3C cone lure under field conditions in south Florida, and that the 2C lures are attractive for up to 8 wk.
Does the use of i-FACTOR bone graft affect bone healing in those undergoing periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH)? A retrospective study
Authors: O’Brien Michael J M , Jones Denise M , Semciw Adam Ivan , Balakumar Jitendra , Grabinski Rafal , Roebert Justin , Coburn Georgia M , Mechlenburg Inger , Kemp Joanne L
Published: June 2022

The aims of this study were to compare, in patients with and without the use of i-FACTOR bone graft during periacetabular osteotomy (PAO) surgery for developmental dysplasia of the hip (DDH), (i) bone healing at six-weeks post-operatively (ii) rate of complications. This was a retrospective review of case records. Participants were people aged 15-50 years undergoing rectus-sparing minimally invasive PAO surgery for DDH. Group 1: patients with i-FACTOR, Group 2: No i-FACTOR. The primary outcome was the rate of bone healing on radiographs at 6 weeks. The likelihood of bone healing was compared using logistic regression with Generalised Estimating Equations (GEE) and expressed as odds ratios (95% confidence intervals (CIs; P < 0.05)). The occurrence of complications was extracted from surgical records. The i-FACTOR group had 3-times greater odds of partial/full union than those without [adjusted odds ratio (95% CIs, P-value)]: [3.265 (1.032 to 10.330, P = 0.044)]. The i-FACTOR group had 89% partial/full union at 6-weeks, compared to 69% of the non-i-FACTOR group. Half of the patients had leaking of bone graft in the i-FACTOR group versus 10% in the non-i-FACTOR group, 26% of the i-FACTOR group and 12% of the non-i-FACTOR group had neuropraxia of the lateral femoral cutaneous nerve (LFCN). Complication rates were low, and similar between groups. However, the rate of LFCN neuropraxia and bone graft leakage was higher in the i-FACTOR. These findings should be confirmed in a future prospective randomised clinical trial and include outcomes such as pain and quality of life.
Brain Cell Senescence: A New Therapeutic Target for the Acute Treatment of Ischemic Stroke
Authors: Baixauli-Martín Júlia , Aliena-Valero Alicia , Castelló-Ruiz María , Burguete María C , López-Morales Mikahela A , Muñoz-Espín Daniel , Torregrosa Germán , Salom Juan B
Published: June 2022

Aging is a major risk factor for cerebral infarction. Since cellular senescence is intrinsic to aging, we postulated that stroke-induced cellular senescence might contribute to neural dysfunction. Adult male Wistar rats underwent 60-minute middle cerebral artery occlusion and were grouped according to 3 reperfusion times: 24 hours, 3, and 7 days. The major biomarkers of senescence: 1) accumulation of the lysosomal pigment, lipofuscin; 2) expression of the cell cycle arrest markers p21, p53, and p16INK4a; and 3) expression of the senescence-associated secretory phenotype cytokines interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were investigated in brain samples. Lipofuscin accumulation was scarce at the initial stage of brain damage (24 hours), but progressively increased until it reached massive distribution at 7 days post-ischemia. Lipofuscin granules (aggresomes) were mainly confined to the infarcted areas, that is parietal cortex and adjacent caudate-putamen, which were equally affected. The expression of p21, p53, and p16INK4a, and that of IL-6, TNF-α, and IL-1β, was significantly higher in the ischemic hemisphere than in the non-ischemic hemisphere. These data indicate that brain cell senescence develops during acute ischemic infarction and suggest that the acute treatment of ischemic stroke might be enhanced using senolytic drugs.
A rare case of small bowel adenocarcinoma complicating coeliac disease
Authors: Mirza Muhammad H , Nzewi Emeka
Published: June 2022

Small bowel adenocarcinoma is an uncommon surgical pathology. Due to non-specific symptoms, most cases present late and pose a challenge to diagnose. We present a case of a small bowel adenocarcinoma in a patient with coeliac disease. A female patient presented to the emergency department with a 3-week history of nausea, anorexia and intermittent bilious vomiting. It was associated with crampy abdominal pain. She was diagnosed with coeliac disease two years ago and commenced on a gluten-free diet. A subsequent computed tomography scan of abdomen and pelvis demonstrated a small bowel stricture with dilated proximal and collapsed distal bowel loops. The stricture was surgically resected followed by primary anastomosis. Histology confirmed adenocarcinoma with nodal metastasis. She received adjuvant chemotherapy and recovered well. In general, small bowel adenocarcinomas are rare and a high index of suspicion is required in patients with predisposing factors e.g. coeliac disease.
Synchronous sinonasal and respiratory papilloma: could long-term positive pressure ventilation be the cause? A rare case report
Authors: Kumar Shivani Angelique , O’Meara Connor , Paulus Felik , Wise Laura , Havas Thomas
Published: June 2022

This case report describes a rare presentation of synchronous pathologies—sinonasal inverted papilloma (SIP) and recurrent respiratory papillomatosis (RRP)—in a 47-year-old man using continuous positive airway pressure (CPAP) ventilation for progressive obstructive sleep apnoea. As far as we know, this is the first case of concurrent SIP and RRP disease described in the literature. The patient initially presented for management of chronic rhinosinusitis symptoms. He was found to have an extensive nasal lesion on flexible nasendoscopy, for which surgical management was recommended. However, during anaesthetic induction, he obstructed unexpectedly and was found to have an occlusive supraglottic lesion that required expedient ENT airway management. Diagnosis was made clinically and was supported with histopathology of excised tissue. Management involved multiple staged procedures for excision of sinonasal and glottic lesions and regular follow-up and imaging.
RiceNCexp: a rice non-coding RNA co-expression atlas based on massive RNA-seq and small-RNA seq data
Authors: Zhang Baoyi , Fei Yuhan , Feng Jiejie , Zhu Xueai , Wang Rui , Xiao Hanqing , Zhang Hongsheng , Huang Ji
Published: June 2022

Non-coding RNAs (ncRNAs) play important roles in regulating expression of protein-coding genes. Although gene expression databases have emerged in a timely manner, a comprehensive expression database for ncRNAs is still lacking. Herein, we constructed a rice ncRNA co-expression atlas (RiceNCexp), based on 491 RNA-seq and 274 small RNA (sRNA)-seq datasets. RiceNCexp hosts four types of ncRNAs, namely lncRNAs, PHAS genes, miRNAs, and phasiRNAs. RiceNCexp provides comprehensive expression information for rice ncRNAs in 22 tissues/organs, an efficient tau-based mining tool for tissue-specific ncRNAs, and the robust co-expression analysis among ncRNAs or between ncRNAs and protein-coding genes, based on 116 pairs of RNA-seq and sRNA-seq libraries from the same experiments. In summary, RiceNCexp is a user-friendly and comprehensive rice ncRNA co-expression atlas and can be freely accessed at https://cbi.njau.edu.cn/RiceNCexp/.
Structured Curricular Change Fails to Combat Resident Burnout
Authors: Halista Courtney E , Dalton Heather A , Thornton Jennifer A
Published: June 2022

Introduction

During the 2020-2021 academic year, the Family Medicine (FM) faculty at David Grant USAF Medical Center (DGMC) incorporated Clinic First principles into the resident educational experience. The faculty hypothesized that these changes could improve symptoms of resident burnout.

Materials and Methods

The study was conducted at a single United States Air Force (USAF) FM residency program in California and was approved by the DGMC Institutional Review Board. The validated Maslach Burnout Inventory Human Services Survey for Medical Personnel was used to assess (1) emotional exhaustion, (2) depersonalization, and (3) personal achievement both prior to and following implementation of the Clinic First-inspired curriculum. Descriptive and inferential statistics were used to summarize the data.

Results

There were 25 eligible FM residents who participated in the study. At baseline, the mean scores on the Maslach Burnout Inventory Human Services Survey for Medical Personnel indicated moderate burnout across all 3 domains. There was a statistically significant difference (P = .03) in the mean EE score over time, demonstrating worsening exhaustion. There was no statistically significant difference (P = .37 and P = .08, respectively) in the mean DP or PA score over time.

Conclusions

Residents in the DGMC FM residency program were experiencing moderate burnout at the beginning of the 2020-2021 AY. Due to unforeseen challenges, the Clinic First initiative was not realized in its full potential, and the curriculum changes did not definitively protect against burnout. Further study is indicated.
The ALMA REBELS Survey: dust continuum detections at z > 6.5
Authors: Inami Hanae , Algera Hiddo S B , Schouws Sander , Sommovigo Laura , Bouwens Rychard , Smit Renske , Stefanon Mauro , Bowler Rebecca A A , Endsley Ryan , Ferrara Andrea , Oesch Pascal , Stark Daniel , Aravena Manuel , Barrufet Laia , da Cunha Elisabete , Dayal Pratika , De Looze Ilse , Fudamoto Yoshinobu , Gonzalez Valentino , Graziani Luca , Hodge Jacqueline A , Hygate Alexander P S , Nanayakkara Themiya , Pallottini Andrea , Riechers Dominik A , Schneider Raffaella , Topping Michael , van der Werf Paul
Published: June 2022

We report 18 dust continuum detections (≥3.3σ) at ∼88 and 158 $\mu{\rm m}$ out of 49 ultraviolet (UV)-bright galaxies (MUV < −21.3 mag) at $z$ > 6.5, observed by the Cycle-7 Atacama Large Millimeter/submillimeter Array (ALMA) Large Program, Reionization-Era Bright Emission Line Survey (REBELS) and its pilot programs. This has more than tripled the number of dust continuum detections known at $z$ > 6.5. Out of these 18 detections, 12 are reported for the first time as part of REBELS. In addition, 15 of the dust continuum detected galaxies also show a [C ii]$_{\rm 158\,{\rm \mu m}}$ emission line, providing us with accurate redshifts. We anticipate more line emission detections from six targets (including three continuum detected targets) where observations are still ongoing. We estimate that all of the sources have an infrared (IR) luminosity (LIR) in a range of $3\!-\!8 \times 10^{11}\, {\rm L_\odot }$, except for one with $L_{\rm IR} = 1.5^{+0.8}_{-0.5} \times 10^{12}\, \, {\rm L_{\odot }}$. Their fraction of obscured star formation is significant at ${\gtrsim} 50{{\ \rm per\ cent}}$, despite being UV-selected galaxies. Some of the dust continuum detected galaxies show spatial offsets (∼0.5–1.5 arcsec) between the rest-UV and far-IR emission peaks. These separations could imply spatially decoupled phases of obscured and unobscured star formation, but a higher spatial resolution observation is required to confirm this. REBELS offers the best available statistical constraints on obscured star formation in UV-luminous galaxies at $z$ > 6.5.
Search for OB associations in Gaia Early Data Release 3
Authors: Chemel Alexander A , de Grijs Richard , Glushkova Elena V , Dambis Andrey K
Published: June 2022

The distribution of young stars into OB associations has long been in need of updating. High-precision Gaia Early Data Release 3 astrometry, coupled with modern machine-learning methods, allows this to be done. We have compiled a well-defined sample which includes OB stars and young open clusters (OCs), in total comprising about 47 700 objects. To break the sample down into groupings resembling associations, we applied the HDBSCAN* clustering algorithm. We used a Monte Carlo method to estimate the kinematic ages of the resulting clusters and the Student’s t-test to assess the significance of the linear correlations between proper motions and coordinates, indicating the presence of possible cluster expansion signatures. The ages of the majority of clusters demonstrating a general expansion at a 1σ confidence level are several tens of Myr, which is in agreement with the expected ages of OB associations. We found 32 OCs which turned out to be members of the resulting groupings; their ages are consistent with one another within the uncertainties. Comparison of the clusters thus obtained with the historical composition of OB associations in the literature shows a correspondence between their positions in the Galaxy but an apparent absence of good one-to-one stellar matches. Therefore, we suggest that the historical composition of OB associations needs to be revised.
OCT4 activates aSuv39h1-repressive antisense lncRNA to couple histone H3 Lysine 9 methylation to pluripotency
Authors: Bernard Laure D , Dubois Agnès , Heurtier Victor , Fischer Véronique , Gonzalez Inma , Chervova Almira , Tachtsidi Alexandra , Gil Noa , Owens Nick , Bates Lawrence E , Vandormael-Pournin Sandrine , Silva José C R , Ulitsky Igor , Cohen-Tannoudji Michel , Navarro Pablo
Published: June 2022

Histone H3 Lysine 9 (H3K9) methylation, a characteristic mark of heterochromatin, is progressively implemented during development to contribute to cell fate restriction as differentiation proceeds. Accordingly, in undifferentiated and pluripotent mouse Embryonic Stem (ES) cells the global levels of H3K9 methylation are rather low and increase only upon differentiation. How global H3K9 methylation levels are coupled with the loss of pluripotency remains largely unknown. Here, we identify SUV39H1, a major H3K9 di- and tri-methylase, as an indirect target of the pluripotency network of Transcription Factors (TFs). We find that pluripotency TFs, principally OCT4, activate the expression of Suv39h1as, an antisense long non-coding RNA to Suv39h1. In turn, Suv39h1as downregulates Suv39h1 transcription in cis via a mechanism involving the modulation of the chromatin status of the locus. The targeted deletion of the Suv39h1as promoter region triggers increased SUV39H1 expression and H3K9me2 and H3K9me3 levels, affecting all heterochromatic regions, particularly peri-centromeric major satellites and retrotransposons. This increase in heterochromatinization efficiency leads to accelerated and more efficient commitment into differentiation. We report, therefore, a simple genetic circuitry coupling the genetic control of pluripotency with the global efficiency of H3K9 methylation associated with a major cell fate restriction, the irreversible loss of pluripotency.
Rationale, Strengths, and Limitations of Real-World Evidence in Oncology: A Canadian Review and Perspective
Authors: Azoulay Laurent
Published: June 2022

Randomized controlled trials (RCTs) continue to be the basis for essential evidence regarding the efficacy of interventions such as cancer therapies. Limitations associated with RCT designs, including selective study populations, strict treatment regimens, and being time-limited, mean they do not provide complete information about an intervention’s safety or the applicability of the trial’s results to a wider range of patients seen in real-world clinical practice. For example, recent data from Alberta showed that almost 40% of patients in the province’s cancer registry would be trial-ineligible per common exclusion criteria. Real-world evidence (RWE) offers an opportunity to complement the RCT evidence base with this kind of information about safety and about use in wider patient populations. It is also increasingly recognized for being able to provide information about an intervention’s effectiveness and is considered by regulators as an important component of the evidence base in drug approvals. Here, we examine the limitations of RCTs in oncology research, review the different types of RWE available in this area, and discuss the strengths and limitations of RWE for complementing RCT oncology data.
Coronitic and Symplectitic Textures in Meta-Troctolite Reveal the Transition from Magmatism to Granulite-Facies Metamorphism in the Early Paleozoic Tongbai Orogen, Central China
Authors: Wang Tingting , Zheng Jianping , Scott James M , Ping Xianquan , Ma Qiang , Xiong Qing , Zhang Sai
Published: June 2022

Newly discovered meta-troctolite enclaves in Early Paleozoic Huanggang diorite within dominantly meta-volcaniclastic greenschist to amphibolite facies Erlangping unit in central China extends the known extent of granulite-facies metamorphism in the Tongbai Orogen. Evidence for this granulite facies event is preserved in coronitic and symplectitic textures developed in the meta-troctolites enclaves. The primary assemblage comprises olivine and plagioclase with minor orthopyroxene, clinopyroxene, spinel and amphibole. The late magmatic stage comprising an orthopyroxene (Opx1) corona around olivine and clinopyroxene corona around spinel formed by reaction of cumulus and intercumulus phases with trapped melt at around 1040–1060°C near the solidus. During troctolite cooling, metamorphic solid-state replacement of primary olivine and plagioclase produced orthopyroxene (Opx1)/clinopyroxene (Cpx1) + vermicular spinel (Sp1) symplectite, followed by an inclusion-free amphibole (Amp1) layer surrounded by amphibole + spinel symplectite (Amp2 + Sp2). Microstructural, pseudosection and mineral isopleth analysis coupled with prominent compositional zoning in the Opx1 corona and chrome-rich spinel (Cr-Sp) suggests that the symplectites formed by diffusion-controlled solid-state replacement at the interface of reactant minerals, probably during cooling to granulite-facies conditions of ~820–880°C and 6.7–7.0 kbar. U–Pb dates of rare metamorphic zircon, as indicated by growth zonation and identification of metamorphic minerals enclosed in grains by Raman probe, are ca. 450 Ma. The reaction textures record the transition from late magmatic to granulite-facies metamorphism with the heat supplied by magma upwelling at the base of Erlangping arc triggered by extension of Erlangping back-arc.
Chain or sphere? Perspectives on colony shapes and sizes in microalgae
Authors: Wang Xiaodong , Tang Kam W
Published: June 2022

Some microalgal species can increase their collective size by forming colonies; notable examples are chained colonies in diatoms and Scenedesmus sp., and spherical colonies in Phaeocystis globosa. For a given cell-specific growth rate, chain formation increases collective length quickly to fend off ciliates, but not against tube- and pallium-feeding heterotrophic dinoflagellates or metazoan grazers with ability to manipulate chains to aid ingestion. Sphere increases in volume relatively slowly but would be difficult to manipulate even for metazoan grazers. Diffusive nutrient supply to a chained colony would be a fixed proportion of that to solitary cells, regardless of chain length, whereas cells within a spherical colony would experience increasing nutrient limitation with increasing colony size. One hemisphere of a spherical colony would inevitably receive less irradiance, creating an auto-light limitation. Experimental data showed that light decreased substantially as it passed through a P. globosa colony, and the optical density of the colony increased linearly with colony diameter. However, neither in situ nutrient nor light limitation alone can explain an order-of-magnitude difference in colony size between the European and the Asian P. globosa populations. Instead, some evidence of different expression of gene(s) involved in colony formation and enlargement suggests genomic variations among the different populations.
Multigenerational Effects of an Environmentally Relevant Phthalate Mixture on Reproductive Parameters and Ovarian miRNA Expression in Female Rats
Authors: Gonsioroski Andressa V , Aquino Ariana M , Alonso-Costa Luiz G , Barbisan Luis F , Scarano Wellerson R , Flaws Jodi A
Published: June 2022

Phthalates are endocrine-disrupting chemicals used in many consumer products. Our laboratory previously developed an environmentally relevant phthalate mixture consisting of 6 phthalates and found that it disrupted female fertility in mice. However, it was unknown if maternal exposure to the mixture affects reproductive parameters and ovarian post-transcription in the F1 and F2 generation of female rats. Thus, we tested the hypothesis that maternal exposure to the phthalate mixture affects folliculogenesis, steroidogenesis, and ovarian microRNA (miRNA) in the F1 and F2 generations of female rats. Pregnant female rats were divided into 4 groups and orally dosed daily from gestational day 10 to postnatal day 21 with corn oil (control group), 20 μg/kg/day, 200 μg/kg/day, or 200 mg/kg/day of the phthalate mixture. Maternal exposure to the phthalate mixture impaired folliculogenesis in the F1 and F2 generations of female rats and affected steroidogenesis in the F1 generation of female rats compared to control. Further, the phthalate mixture altered ovarian expression of some genes related to the cell cycle and steroidogenesis compared to control in the F1 and F2 generations of female rats. The mixture also increased ovarian expression of rno-mir-184 that is involved with the oocyte maturation process. Collectively, our data show that maternal exposure to the phthalate mixture affects folliculogenesis and steroidogenesis in the F1 and F2 generations of female rats and alters ovarian miRNA expression in the F1 generation of female rats.
Transcriptomic Identification of a Unique Set of Nodule-Specific Cysteine-Rich Peptides Expressed in the Nitrogen-Fixing Root Nodule of Astragalus sinicus
Authors: Wei Feng , Liu Yuan , Zhou Donglai , Zhao Wenlong , Chen Zhennan , Chen Dason , Li Youguo , Zhang Xue-Xian
Published: June 2022

Legumes in the inverted repeat-lacking clade (IRLC) each produce a unique set of nodule-specific cysteine-rich (NCR) peptides, which act in concert to determine the terminal differentiation of nitrogen-fixing bacteroid. IRLC legumes differ greatly in their numbers of NCR and sequence diversity. This raises the significant question how bacteroid differentiation is collectively controlled by the specific NCR repertoire of an IRLC legume. Astragalus sinicus is an IRLC legume that forms indeterminate nodules with its microsymbiont Mesorhizobium huakuii 7653R. Here, we performed transcriptome analysis of root and nodule samples at 3, 7, 14, 28 days postinoculation with M. huakuii 7653R and its isogenic ∆ bacA mutant. BacA is a broad-specificity peptide transporter required for the host-derived NCRs to target rhizobial cells. A total of 167 NCRs were identified in the RNA transcripts. Comparative sequence and electrochemical analysis revealed that A. sinicus NCRs (AsNCRs) are dominated by a unique cationic group (termed subgroup C), whose mature portion is relatively long (>60 amino acids) and phylogenetically distinct and possessing six highly conserved cysteine residues. Subsequent functional characterization showed that a 7653R variant harboring AsNCR083 (a representative of subgroup C AsNCR) displayed significant growth inhibition in laboratory media and formed ineffective white nodules on A. sinicus with irregular symbiosomes. Finally, bacterial two-hybrid analysis led to the identification of GroEL1 and GroEL3 as the molecular targets of AsNCR067 and AsNCR076. Together, our data contribute to a systematic understanding of the NCR repertoire associated with the A. sinicus and M. huakuii symbiosis.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Updates in the treatment of gonococcal infections
Authors: Urnoski Eric , Patterson Michelle Link
Published: June 2022

This article highlights important changes in treatment of gonococcal infections secondary to rising infection rates, as well as increased drug-resistance to previous therapy recommendations. The article is intended to assist clinicians in both the ambulatory as well as inpatient setting when treating patients with sexually transmitted infections.
Safety of combining dabrafenib plus trametinib in elderly BRAF V600 mutation-positive advanced melanoma patients: real-world data analysis of Spanish patients (ELDERLYMEL)
Authors: González-Barrallo Inés , Castellón Rubio Victoria Eugenia , Medina Javier , España Sofia , Mujika Karmele , Majem Margarita , Aguado Carlos , Cabrera Suárez Miguel Ángel , Palacio Isabel , Osterloh Lisa , Martínez-Fernández Alejandro , García-Castaño Almudena
Published: June 2022

Efficacy and safety of dabrafenib and trametinib in metastatic melanoma have been demonstrated in two-phase III and one-phase I/II clinical trials. However, patients at least 75 years old (y.o.) were largely underrepresented. Additionally, the safety profile of dabrafenib and trametinib based on age is unknown. ELDERLYMEL is a retrospective noninterventional multicenter study, describing the effectiveness and safety of at least 75 y.o. patients compared with less than 75 y.o. patients with advanced BRAF V600-mutated melanoma treated with dabrafenib plus trametinib or dabrafenib monotherapy. A total of 159 patients were included, 130 less than 75 y.o. and 29 at least 75 y.o. Clinical features were similar between the groups, except in the number of comorbidities, number of metastatic sites, Eastern Cooperative Oncology Group (ECOG) performance status, and BRAF V600-mutation type. Five patients per group received dabrafenib monotherapy. There were no differences in adverse events (AEs) rate or grade between the groups. However, AE profiles were different between the groups, being pyrexia infrequent in patients at least 75 y.o. (13.8% vs. 42.3%; P = 0.005). Dabrafenib and trametinib dose intensities were lower in at least 75 y.o. patients (P = 0.018 and P = 0.020), but there were no differences in effectiveness between the groups. Finally, in a multivariate analysis, sex (female) was the only variable independently associated with an increased risk of AE grade ≥3. Data from the ELDERLYMEL study demonstrate that dabrafenib plus trametinib is safe and effective in at least 75 y.o. patients with advanced BRAF V600-mutated melanoma without increasing toxicity. Additionally, we describe a different safety profile depending on age and sex.
Scaling up preexposure prophylaxis to maximize HIV prevention impact
Authors: Grulich Andrew E. , Bavinton Benjamin R.
Published: June 2022

Purpose of review

Ten years since the first regulatory approval of oral HIV preexposure prophylaxis (PrEP), this review summarizes PrEP uptake, the role of ambitious PrEP targets, emerging evidence of impact on the HIV epidemic and innovative approaches to increasing PrEP uptake.

Recent findings

PrEP uptake among people at risk of HIV has been slow, but has accelerated in recent years, particularly in gay and bisexual men in a limited number of high-income settings and recently in heterosexuals at risk of HIV in sub-Saharan Africa. However, UNAIDS 2020 PrEP targets and HIV prevention targets were missed by large margins. Although UNAIDS testing and treatment targets have galvanised public health action, in contras, PrEP targets have been lower profile and insufficiently ambitious. Parts of the USA, Australia and the UK with high PrEP coverage have demonstrated striking reductions in HIV infection at the population level, as PrEP is introduced at scale. Scaling up PrEP uptake will require innovations in PrEP promotion, simplified models of care, improved adherence interventions, improved choice in the form of longer-acting PrEP and interventions to ensure that all those who can benefit from PrEP can access it.

PrEP is a revolutionary HIV prevention tool, which if ambitiously scaled up could drive HIV transmission towards elimination. Highly publicized and ambitious PrEP targets could help drive this.