bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract

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 &lt; .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 &lt; .0001) and to develop seropositive immunoglobulin G (IgG) (8 vs 10 days; HR, 10.78; 95% CI, 9.98–11.58; P &lt; .0001). All adverse events resolved upon follow-up. Combination group (HR, 4.1 95% CI, 1.9–8.6, P &lt; .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

Abstract

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

AbstractNatural 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

Abstract

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 = &lt;.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

Abstract

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 &lt; 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

Abstract

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 &lt;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

Abstract
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

ABSTRACT
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 &lt; 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

Abstract
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

Abstract
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

Abstract
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.