bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiling of pemphigus lesion infiltrating mononuclear cells reveals a distinct local immune microenvironment and novel lncRNA regulators
Authors: Huang Zi-xuan , Qu Peng , Wang Kan-kan , Zheng Jie , Pan Meng , Zhu Hai-qin 
Published: April 2022

AbstractPemphigus is an autoimmune skin disease. Ectopic lymphoid-like structures (ELSs) were found to be commonly present in the pemphigus lesions, presumably supporting in situ desmoglein (Dsg)-specific antibody production. Yet functional phenotypes and the regulators of Lymphoid aggregates in pemphigus lesions remain largely unknown. Herein, we used microarray technology to profile the gene expression in skin lesion infiltrating mononuclear cells (SIMC) from pemphigus patients. On top of that, we compared SIMC dataset to peripheral blood mononuclear cells (PBMC) dataset to characterize the unique role of SIMC. Functional enrichment results showed that mononuclear cells in skin lesions and peripheral blood both had over-represented IL-17 signaling pathways while neither was characterized by an activation of type I Interferon signaling pathways. Cell-type identification with relative subsets of known RNA transcripts (CIBERSORT) results showed that naïve natural killer cells (NK cells) were significantly more abundant in pemphigus lesions, and their relative abundance positively correlated with B cells abundance. Meanwhile, plasma cells population highly correlated with type 1 macrophages (M1) abundance. In addition, we also identified a lncRNA LINC01588 which might epigenetically regulate T helper 17 cells (Th17)/regulatory T cells (Treg) balance via the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Here, we provide the first transcriptomic characterization of lesion infiltrating immune cells which illustrates a distinct interplay network between adaptive and innate immune cells. It helps discover new regulators of local immune response, which potentially will provide a novel path forward to further uncover pemphigus pathological mechanisms and develop targeted therapy.
The prevalence and genotype distribution of human papillomavirus among women in Guangxi, southern China
Authors: Wei Liuting , Ma Liping , Qin Lingyan , Huang Zhihu 
Published: April 2022

Abstract
Background
Human papillomavirus is a primary cause of cervical cancer and genital warts. HPV vaccine can prevent high-grade cervical lesions as well as cervical cancer. The aim of this study was to analyze the prevalence and genotype distribution of human papillomavirus among women in Guangxi before and after the HPV vaccine was approved for use in China.

Methods
From January 2016 to May 2021, 41,140 women were tested for HPV infection. HPV genotyping included 15 high-risk HPV (HR-HPV) and 6 low-risk HPV (LR-HPV) genotypes. Total prevalence, annual trend, and specific age group prevalence and genotype distribution were analyzed.

Results
The overall HPV infection rate was 18.10% among Guangxi women self-referred to clinic for gynecologic problems in southern China. During 2016–2018, the prevalence of HPV infection showed an upward trend, from 18.21% in 2016 to 21.99% in 2018, and later it showed a downward trend, from 18.35% in 2019 to 12.26% in May 2021. Pure HR-HPV genotypes (14.36%) were found in more infections than pure LR-HPV genotypes (2.77%) and mixed genotypes (0.97%). Two peaks of HPV infection were found in the ≤ 25 years (22.94%) and 56–65 years (21.25%) groups. The six most prevalent HR-HPV genotypes were HPV 52 (4.06%), 16 (2.70%), 58 (2.24%), 51 (1.87%), 39 (1.52%), and 53 (1.52%). The three most prevalent LR-HPV genotypes were HPV 6 (1.31%), CP8304 (1.01%), and 11 (0.82%). Infection with a single HR-HPV genotype was the most common type of infection, with an overall infection rate of 12.30%. Infection with two HPV genotypes was the most common multiple HR-HPV infection type, with an infection rate of 2.35%.

Conclusions
The cervical HPV infection rate of women in Guangxi is very high, and there is significant age specificity. There is a need to increase HPV vaccination of young people and the screening of middle-aged and elderly people.
Challenging the dogma to “always operate” acute hip fractures: a proof-of-concept pilot study for nonoperative management of undisplaced femoral neck fractures
Authors: Vinas-Rios Juan Manuel , Wölm Jan-Henning , Sellei Richard Martin , Ladenburger Andreas 
Published: April 2022

AbstractBackgroundThe notion that all acute hip fractures are a surgical entity requiring either surgical fracture fixation or hip replacement represents a historic dogma, particularly within the orthopaedic community of the United States. The present study from a European regional trauma center was designed to challenge the notion that stable and undisplaced femoral neck fractures represent an absolute indication for surgical management.MethodsThe purpose of this study was to investigate the hypothesis that stable and undisplaced femoral neck fractures of the Garden types 1 and 2 can be safely managed nonoperatively. A retrospective observational cohort study was carried out at a regional orthopaedic trauma center in Germany from January 1, 2016 to June 30, 2021. The inclusion criteria specified patients older than 18 years suffering a < 24 h, traumatic, femoral neck fracture Garden types 1 and 2. Exclusion criteria included Garden types 3 and 4 femoral neck fractures, pregnancy, active infection or previous surgery, tumor-associated fractures, medical history of femoral neck necrosis, vascular injury associated with femoral neck fractures, nerve injury associated to a femoral neck fracture and ≥ 24 h femoral neck fracture. The primary intention of this research was to identify deterioration of fracture retention with an ensuing unplanned trip to the operating room in femoral neck fractures Garden types 1 and 2. Secondary were included unplanned readmissions and complications such as surgical site infection.ResultsA total of 41 undisplaced femoral neck fractures (Garden types 1 and 2) were included in this study;n = 20 were in the resulting admission operatively treated (group 1) andn = 21 were treated conservatively. The mean age in group 1 was 76 years; women (70%). In group 2 it was 81 years with a female dominance (71.4%). Admission status: Garden types 1 and 2, group 1n = 13/7 and group 2n = 15/6. Subsequent femoral neck fracture displacement (Y/N) (in case of operation, before operation) group 1n = 14/6 and group 2n = 6/15.ConclusionAccording with our results, patients sustaining Garden type 1 femoral neck fractures, depending on age and comorbidities, should be treated conservatively with weight bearing and under physiotherapeutic instructions. In case of femoral neck fractures Garden type 2, a surgical treatment should be performed in order to avoid femoral neck fractures to slip after weight bearing by lacking of fracture impaction.
Verrucae pedis in children with juvenile idiopathic arthritis and other paediatric rheumatic diseases: a cross‐sectional study
Authors: Ferrari Jill 
Published: April 2022

AbstractBackgroundVerrucae pedis (verrucae / VPs) are a common viral infection of the skin seen in children. There are limited studies of the prevalence, duration and impact of verrucae pedis in children who are immunosuppressed. The studies available suggest that, in these children, the warts are more widespread and are more long‐standing. The primary aim of this study was to determine the prevalence of verrucae pedis in children attending rheumatology clinics who may have some degree of immunosuppression due to their prescribed medication and compare this to the reported prevalence in the healthy population.MethodChildren attending out‐patient rheumatology appointments were recruited. The young people were aged between four and 17 years old. A visual inspection of both feet was used to identify potential verrucae. Diagnosis of a verruca pedis was confirmed on observation of the typical clinical features. The location, duration of presence, previous treatments, presence of verrucae in other family members and psychological impact was recorded.ResultsA total of 71 children were included. Of the group, 55 children had no verrucae present, 16 children had one or more verrucae. The prevalence of verrucae was 22.5%. Medication impacting on the immune system was prescribed in 80% of the group. There appeared to be no greater chance of having verrucae if taking immunosuppressive medication than compared to having no medication (OR = 1.1, 95%CI 0.26 to 4.48, p = 0.46). Children with verrucae tended to be between 9 and 12 years old. In total, 37.5% of the young people with verrucae had lesions reportedly present for 24 months or more. Two‐thirds of the participants were not concerned about verrucae being present and most participants with a verruca were not aware of what a verruca was, but despite this the majority of participants (81%) had sought treatment for the verrucae.ConclusionChildren with Juvenile Idiopathic Arthritis and other rheumatic conditions have no greater prevalence of verrucae compared to the general population. The verrucae present were of a similar clinical type and did not seem to be more widespread or have atypical features, which has been reported in other immunocompromised populations. The percentage of lesions remaining beyond 24 months was found to be slightly greater than has been reported in other healthy populations. The children in this study seemed to be less emotionally concerned about their verrucae, despite this most families had sought treatment for the verrucae.
Earlier point-of-care ultrasound, shorter length of stay in patients with acute flank pain
Authors: Wang Pei-Hsiu , Chen Jia-Yu , Ling Dean-An , Lee An-Fu , Ko Ying-Chih , Lien Wan-Ching , Huang Chien-Hua 
Published: April 2022

Abstract
Background
The effects of early integration of point-of-care ultrasound (PoCUS) into patient care are uncertain. This study aims to investigate the effects of early PoCUS on patients with acute flank pain.

Methods
Adult non-traumatic patients with acute flank pain receiving PoCUS were enrolled. Expert physicians reviewed the medical records and made the “final diagnosis” for the cause of acute flank pain. The primary outcome was the relationship between the door to ultrasound (US) time and length of stay (LOS). The secondary outcomes included the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the sonographic diagnosis, compared with the final diagnosis.

Results
Eight hundred and eighty-eight patients were included in the analysis. Patients receiving early PoCUS (≤120 min) had a shorter LOS (128 vs. 217 min, p < 0.0001). Patients in the late POCUS group (> 120 min) had a trend to receive more CT scans. The disease distribution, sensitivity, specificity, PPV, and NPV were similar in patients receiving early or late PoCUS for target diagnoses. After adjusting for the confounders, early PoCUS (OR, 2.77, 95% CIs, 1.93–3.98) had a positive impact on shorter LOS. In addition, the effect of early PoCUS became more prominent (OR, 4.91, 95% CIs, 3.39–7.13) on LOS in less than 3 h.

Conclusions
Early integration of PoCUS is significantly related to shorter LOS in patients with acute flank pain without increasing morbidity and mortality. Our results suggested “PoCUS early” in these patients to possibly alleviate emergency department crowding.
Trial registration NCT04149041 at the ClinicalTrial.gov.
Identifying clinical subtypes in sepsis-survivors with different one-year outcomes: a secondary latent class analysis of the FROG-ICU cohort
Authors: Soussi Sabri , Sharma Divya , Jüni Peter , Lebovic Gerald , Brochard Laurent , Marshall John C. , Lawler Patrick R. , Herridge Margaret , Ferguson Niall , Del Sorbo Lorenzo , Feliot Elodie , Mebazaa Alexandre , Acton Erica , Kennedy Jason N. , Xu Wei , Gayat Etienne , Dos Santos Claudia C. ,   the FROG-ICU, Soussi Sabri , Mebazaa Alexandre , Gayat Etienne ,   CCCTBG trans-trial group study for InFACT - the International Forum for Acute Care Trialists, Soussi Sabri , Brochard Laurent , Marshall John C. , Herridge Margaret , Dos Santos Claudia C. 
Published: April 2022

Abstract
Background
Late mortality risk in sepsis-survivors persists for years with high readmission rates and low quality of life. The present study seeks to link the clinical sepsis-survivors heterogeneity with distinct biological profiles at ICU discharge and late adverse events using an unsupervised analysis.

Methods
In the original FROG-ICU prospective, observational, multicenter study, intensive care unit (ICU) patients with sepsis on admission (Sepsis-3) were identified (N = 655). Among them, 467 were discharged alive from the ICU and included in the current study. Latent class analysis was applied to identify distinct sepsis-survivors clinical classes using readily available data at ICU discharge. The primary endpoint was one-year mortality after ICU discharge.

Results
At ICU discharge, two distinct subtypes were identified (A and B) using 15 readily available clinical and biological variables. Patients assigned to subtype B (48% of the studied population) had more impaired cardiovascular and kidney functions, hematological disorders and inflammation at ICU discharge than subtype A. Sepsis-survivors in subtype B had significantly higher one-year mortality compared to subtype A (respectively, 34% vs 16%, p < 0.001). When adjusted for standard long-term risk factors (e.g., age, comorbidities, severity of illness, renal function and duration of ICU stay), subtype B was independently associated with increased one-year mortality (adjusted hazard ratio (HR) = 1.74 (95% CI 1.16–2.60); p = 0.006).

Conclusions
A subtype with sustained organ failure and inflammation at ICU discharge can be identified from routine clinical and laboratory data and is independently associated with poor long-term outcome in sepsis-survivors.
Trial registration NCT01367093; https://clinicaltrials.gov/ct2/show/NCT01367093.

Graphical Abstract
Predicting RNA splicing from DNA sequence using Pangolin
Authors: Zeng Tony , Li Yang I 
Published: April 2022

AbstractRecent progress in deep learning has greatly improved the prediction of RNA splicing from DNA sequence. Here, we present Pangolin, a deep learning model to predict splice site strength in multiple tissues. Pangolin outperforms state-of-the-art methods for predicting RNA splicing on a variety of prediction tasks. Pangolin improves prediction of the impact of genetic variants on RNA splicing, including common, rare, and lineage-specific genetic variation. In addition, Pangolin identifies loss-of-function mutations with high accuracy and recall, particularly for mutations that are not missense or nonsense, demonstrating remarkable potential for identifying pathogenic variants.
STRONG for Surgery & Strong for Life — against all odds: intensive prehabilitation including smoking, nutrition, alcohol and physical activity for risk reduction in cancer surgery — a protocol for an RCT with nested interview study (STRONG-Cancer)
Authors: Tønnesen Hanne , Lydom Line Noes , Joensen Ulla Nordström , Egerod Ingrid , Pappot Helle , Lauridsen Susanne Vahr 
Published: April 2022

AbstractBackgroundThere is a large unused potential for risk reduction in the preoperative period via effective lifestyle intervention targeting co-existing risky lifestyles: Smoking, malNutrition, obesity, risky Alcohol intake and insufficient Physical activity (SNAP).This trial compares the efficacy of the integrated STRONG programme with standard care on preoperative risk reduction and secondly on SNAP factor improvement and frailty, postoperative complications and quality of life. A nested interview study explores the patient preferences and the multi-perspective view of patients, relatives and health professionals.MethodsIn total, 42 surgical patients with ≥1 SNAP factor are allocated to individually tailored STRONG programme or usual care during adjuvant chemotherapy prior to radical bladder cancer surgery. The STRONG programme has ≥6 weekly sessions with patient education, motivational and pharmaceutical support. It is based on intensive smoking and alcohol cessation interventions reporting perioperative quit rates > 50%.Surgical risk reduction is measured as ≥1 step for 1 or more risky lifestyles on the ASA-score, secondly as having no risky SNAP factors, and as any SNAP improvement. The outcomes are validated by measurements and biomarkers. Postoperative complications are categorised according to the Clavien-Dindo classification. Health-related quality of life is measured by EQ-5D.The patients are followed up after 6 weeks at surgery and 6 weeks and 6 months postoperatively.A representative sample of the participants, their relatives and the clinical staff are interviewed until data saturation. Transcription, triangulated analyses and data management are conducted using NVivo computer software.DiscussionThe surgical agenda is characterised by fixed dates for surgery focusing on clear risk reduction within a short time. This requires a clinical useful lifestyle intervention programme with a high effect and coverage as well as containing all SNAP factors and tailored to individual needs.The STRONG programme seems to meet these requirements. After development in multi-professional collaboration, STRONG is delivered by a specially trained nurse as part of the surgical patient journey.Overall, this study will bring important new knowledge about risk reduction in a frail patient group undergoing major cancer surgery.Trial registrationRegistration atwww.clintrials.gov(NCT04088968)The manuscript form fromhttps://trialsjournal.biomedcentral.com/bmc/journaland the SPIRIT guidelines are followed.
Stable transformation of fluorescent proteins into Nosema bombycis by electroporation
Authors: Dong Zhanqi , Gao Na , Deng Boyuan , Huang Xuhua , Hu Congwu , Chen Peng , Wu Qin , Lu Cheng , Pan Minhui 
Published: April 2022

AbstractBackgroundMicrosporidia are a group of intracellular parasitic eukaryotes, serious pathogens that cause widespread infection in humans, vertebrates, and invertebrates. Because microsporidia have a thick spore wall structure, the in vitro transformation, cell culture, and genetic operation technology of microsporidia are far behind that of other parasites.MethodsIn this study, according to an analysis of the life-cycle of microsporidia,Nosema bombycis, and different electro-transformation conditions, the transduction efficiency of introducing foreign genes intoN. bombyciswas systematically determined.ResultsWe analyzed the direct electro-transformation of foreign genes into germinatingN. bombycisusing reporters under the regulation of different characteristic promoters. Furthermore, we systematically determined the efficiency of electro-transformation intoN. bombycisunder different electro-transformation conditions and different developmental stages through an analysis of the whole life-cycle ofN. bombycis. These results revealed that foreign genes could be effectively introduced through a perforation voltage of 100 V pulsed for 15 ms during the period ofN. bombycissporeplasm proliferation.ConclusionsWe present an effective method for electro-transformation of a plasmid encoding a fluorescent protein intoN. bombycis, which provides new insight for establishing genetic modifications and potential applications in these intracellular parasites.Graphical Abstract
Ornithodoros (Pavlovskyella) ticks associated with a Rickettsia sp. in Pakistan
Authors: Ali Abid , Numan Muhammad , Khan Mehran , Aiman Ome , Muñoz-Leal Sebastián , Chitimia-Dobler Lidia , Labruna Marcelo B. , Nijhof Ard M. 
Published: April 2022

Abstract
Background
Soft ticks (Ixodida: Argasidae) are medically important ectoparasites that mainly feed on birds and mammals, which play a key role in their geographic distribution and dispersion. Despite their importance, studies on soft ticks are scarce for many regions and countries of the world, including Pakistan.

Methods
In this study, 2330 soft ticks—179 larvae (7.7%), 850 nymphs (36.4%), 711 males (30.5%) and 590 females (25.3%)—were collected from animal shelters in 18 locations within five districts of Khyber Pakhtunkhwa, Pakistan. A subset of the collected ticks was processed for DNA extraction and polymerase chain reaction (PCR) for the amplification of tick 12S ribosomal DNA (rDNA), 16S rDNA and cytochrome c oxidase subunit I (cox1), and rickettsial 16S rDNA gene fragments. The obtained sequences were used for the construction of a phylogenetic tree.

Results
All the specimens were morphologically identified as Ornithodoros, and were morphologically similar to Ornithodoros tholozani. The genus was confirmed by sequencing partial 12S rDNA, 16S rDNA and cox1 gene fragments. Additionally, a Rickettsia sp. was detected in some of the collected ticks by PCR targeting 16S rDNA. The morphological relatedness of the tick specimens with O. tholozani was confirmed by phylogenetic analysis, in which the Ornithodoros sp. clustered with Ornithodoros tholozani and Ornithodoros verrucosus, both of which belong to the subgenus Pavlovskyella and have been previously reported from Israel, Ukraine and Iran. The phylogenetic tree also indicated that the Ornithodoros sp. from Pakistan corresponds to an undetermined species. Furthermore, the associated Rickettsia sp. grouped with the limoniae group of Rickettsia species previously reported from Argas japonicus ticks from China.

Conclusions
This is the first molecular study of an Ornithodoros species from Pakistan. Further studies are essential to confirm its identity and possible pathogenicity with regard to its associated microorganisms in the studied region.

Graphical abstract