bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond
Authors: Gavriilaki Eleni , de Latour Régis Peffault , Risitano Antonio Maria 
Published: September 2021

Abstract
Complement is an elaborate system of innate immunity. Genetic variants and autoantibodies leading to excessive complement activation are implicated in a variety of human diseases. Among them, the hematologic disease paroxysmal nocturnal hemoglobinuria (PNH) remains the prototypic model of complement activation and inhibition. Eculizumab, the first-in-class complement inhibitor, was approved for PNH in 2007. Addressing some of the unmet needs, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan, have also now been approved for PNH. Novel agents, such as factor B and factor D inhibitors, are under study, with very promising results. In this era of several approved targeted complement therapeutics, selection of the proper drug must be based on a personalized approach. Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease, primarily with the C1s inhibitor of the classical complement pathway sutimlimab, as well as with pegcetacoplan. Furthermore, C5 inhibition with eculizumab and ravulizumab, as well as inhibition of the lectin pathway with narsoplimab, is being investigated in transplantation-associated thrombotic microangiopathy. With this revolution of next-generation complement therapeutics, additional hematologic entities, such as delayed hemolytic transfusion reaction or immune thrombocytopenia, might also benefit from complement inhibitors. Therefore, this review aims to describe state-of-the-art knowledge of targeting complement in hematologic diseases, focusing on (1) complement biology for the clinician, (2) complement activation and therapeutic inhibition in prototypic complement-mediated hematologic diseases, (3) hematologic entities under investigation for complement inhibition, and (4) other complement-related disorders of potential interest to hematologists.
Expression of proposed methionine transporters along the gastrointestinal tract of pigs and their regulation by dietary methionine sources
Authors: Romanet Stella , Aschenbach Jörg R. , Pieper Robert , Zentek Jürgen , Htoo John K. , Whelan Rose A. , Mastrototaro Lucia 
Published: September 2021

Abstract
Background
Given the key role of methionine (Met) in biological processes like protein translation, methylation, and antioxidant defense, inadequate Met supply can limit performance. This study investigated the effect of different dietary Met sources on the expression profile of various Met transporters along the gastrointestinal tract (GIT) of pigs.

Methods
A total of 27 pigs received a diet supplemented with 0.21% DL-Met, 0.21% L-Met, or 0.31% DL-2-hydroxy-4-(methylthio)butanoic acid (DL-HMTBA). Changes in mRNA expression of B0AT1, ATB0,+, rBAT, ASCT2, IMINO, LAT4, y+LAT1, LAT2, and SNAT2 were evaluated in the oral mucosa, cardia, fundus, pylorus, duodenum, proximal jejunum, middle jejunum, ileum, cecum, proximal colon, and distal colon, complemented by protein expression analysis of B0AT1, ASCT2, LAT2, and LAT4.

Results
Expression of all investigated transcripts differed significantly along the GIT. B0AT1, rBAT, y+LAT1, LAT2, and LAT4 showed strongest mRNA expression in small intestinal segments. ASCT2, IMINO, and SNAT2 were similarly expressed along the small and large intestines but expression differed in the oral mucosa and stomach. ATB0,+ showed highest mRNA expression in large intestinal tissues, cardia, and pylorus. In pigs fed DL-Met, mRNA expression of ASCT2 was higher than in pigs fed DL-HMTBA in small intestinal tissues and mRNA expression of IMINO was lower than in pigs fed L-Met in large intestinal tissues. Dietary DL-HMTBA induced a stronger mRNA expression of basolateral uptake systems either in the small (LAT2) or large (y+LAT1) intestine. Protein expression of B0AT1 was higher in the middle jejunum and ileum in pigs fed DL-Met when compared with the other Met supplements. LAT4 expression was higher in pigs fed DL-HMTBA when compared with DL-Met (small intestine) and L-Met (small intestine, oral mucosa, and stomach).

Conclusion
A high expression of several Met transporters in small intestinal segments underlines the primary role of these segments in amino acid absorption; however, some Met transporters show high transcript and protein levels also in large intestine, oral mucosa, and stomach. A diet containing DL-Met has potential to increase apical Met transport in the small intestine, whereas a diet containing DL-HMTBA has potential to increase basolateral Met transport in the small intestine and, partly, other gastrointestinal tissues.
Genotype-environment interaction and stability of fiber properties and growth traits in triploid hybrid clones of Populus tomentosa
Authors: Wu Jian , Zhou Qing , Sang Yaru , Kang Xiangyang , Zhang Pingdong 
Published: September 2021

Abstract
Background
Clones provide a sensitive method for evaluating genotypic stability and detecting genotype-environment (G × E) interactions because of non-additive genetic effects among clones and there being no genetic effect among ramets of an ortet. With this study, we aimed to confirm and expand earlier findings, estimate stability parameters, and provide accurate estimates of clonal repeatabilities and genetic gains for a triploid breeding program of P. tomentosa Carr.

Results
Six 5-year-old clonal trials established in Northern China were used to determine the clonal variation, clone × site interactions, and the stability parameters of fiber properties of wood and growth traits. 360 trees from ten hybrid clones were collected from six sites. The clonal and site effects had a highly significant effect (P < 0.001) for all studied traits. While the clone × site interactions had a highly significant effect (P < 0.001) on fiber length (FL), coarseness (C), and tree growth (tree height [H], diameter at breast height [DBH] and stem volume [SV]), and a moderate effect (P < 0.05) on fiber width (FW) and fiber length/width (FL/W). For FL and SV, most of the triploid hybrid clones had higher reaction norms to the improvement in growth conditions and higher phenotypic plasticity. The estimated clonal repeatability of FW (0.93) was slightly higher than for FL (0.89), FL/W (0.83), C (0.91), DBH (0.76), H (0.85), and SV (0.80). Three clonal testing sites were sufficient to estimate quantitative parameters of fiber properties, however, more clonal testing sites would help improve the accuracy of quantitative parameters of the growth traits.

Conclusions
Our results highlight that accurate estimation of quantitative parameters for growth traits in triploid hybrid clones of P. tomentosa requires more clonal testing sites than the fiber properties.
Is obstructive sleep apnoea associated with hypoxaemia and prolonged ICU stay after type A aortic dissection repair? A retrospective study in Chinese population
Authors: Xi Xin , Chen Yu , Ma Wei-Guo , Xie Jiang , Liu Yong-Min , Zhu Jun-Ming , Gong Ming , Zhu Guang-Fa , Sun Li-Zhong 
Published: September 2021

Abstract
Background
Although obstructive sleep apnoea (OSA) is prevalent among patients with aortic dissection, its prognostic impact is not yet determined in patients undergoing major vascular surgery. We aimed to investigate the association of OSA with hypoxaemia and with prolonged intensive care unit (ICU) stay after type A aortic dissection (TAAD) repair.

Methods
This retrospective study continuously enrolled 83 patients who underwent TAAD repair from January 1 to December 31, 2018. OSA was diagnosed by sleep test and defined as an apnoea hypopnea index (AHI) of ≥ 15/h, while an AHI of > 30/h was defined severe OSA. Hypoxaemia was defined as an oxygenation index (OI) of < 200 mmHg. Prolonged ICU stay referred to an ICU stay of > 72 h. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of postoperative OI for prolonged ICU stay. Multivariate logistic regression was performed to assess the association of OSA with hypoxaemia and prolonged ICU stay.

Results
A total of 41 (49.4%) patients were diagnosed with OSA using the sleep test. Hypoxaemia occurred postoperatively in 56 patients (67.5%). Postoperatively hypoxaemia developed mostly in patients with OSA (52.4% vs. 83.0%, p = 0.003), and particularly in those with severe OSA (52.4% vs. 90.5%, p = 0.003). The postoperative OI could fairly predict a prolonged ICU stay (area under the receiver-operating characteristic curve, 0.72; 95% confidence intervals [CI] 0.60–0.84; p = 0.002). Severe OSA was associated with both postoperative hypoxaemia (odds ratio [OR] 6.65; 95% CI 1.56–46.26, p = 0.008) and prolonged ICU stay (OR 5.58; 95% CI 1.54–20.24, p = 0.009).

Conclusions
OSA was common in patients with TAAD. Severe OSA was associated with postoperative hypoxaemia and prolonged ICU stay following TAAD repair.
Applying a novel approach to scoping review incorporating artificial intelligence: mapping the natural history of gonorrhoea
Authors: Whelan Jane , Ghoniem Mohammad , Médoc Nicolas , Apicella Mike , Beck Ekkehard 
Published: September 2021

Abstract
Background
Systematic and scoping literature searches are increasingly resource intensive. We present the results of a scoping review which combines the use of a novel artificial-intelligence-(AI)-assisted Medline search tool with two other ‘traditional’ literature search methods. We illustrate this novel approach with a case study to identify and map the range of conditions (clinical presentations, complications, coinfections and health problems) associated with gonorrhoea infection.

Methods
To fully characterize the range of health outcomes associated with gonorrhoea, we combined a high yield preliminary search with a traditional systematic search, then supplemented with the output of a novel AI-assisted Medline search tool based on natural language processing methods to identify eligible literature.

Results
We identified 189 health conditions associated with gonorrhoea infection of which: 53 were identified through the initial ‘high yield’ search; 99 through the systematic search; and 124 through the AI-assisted search. These were extracted from 107 unique references and 21 International Statistical Classification of Diseases and Related Health Problems Ninth and Tenth Revision (ICD 9/10) or Read codes. Health conditions were mapped to the urogenital tract (n = 86), anorectal tract (n = 6) oropharyngeal tract (n = 5) and the eye (n = 14); and other conditions such as systemic (n = 61) and neonatal conditions (n = 7), psychosocial associations (n = 3), and co-infections (n = 7). The 107 unique references attained a Scottish Intercollegiate Guidelines Network (SIGN) score of ≥ 2++ (n = 2), 2+ (14 [13%]), 2- (30 [28%]) and 3 (45 [42%]), respectively. The remaining papers (n = 16) were reviews.

Conclusions
Through AI screening of Medline, we captured – titles, abstracts, case reports and case series related to rare but serious health conditions related to gonorrhoea infection. These outcomes might otherwise have been missed during a systematic search. The AI-assisted search provided a useful addition to traditional/manual literature searches especially when rapid results are required in an exploratory setting.
Restarting elective endoscopy safely amidst an evolving pandemic and the impact of patient perception
Authors: Nguyen Christopher , Kline Kevin T. , Merwat Shehzad , Merwat Sheharyar , Luthra Gurinder , Parupudi Sreeram , Cohn Steven 
Published: September 2021

Abstract
Background
The COVID-19 pandemic has led to disruptions in elective and outpatient procedures. Guidance from the Centers for Medicare and Medicaid Services provided a framework for gradual reopening of outpatient clinical operations. As the infrastructure to restart endoscopy has been more clearly described, patient concerns regarding viral transmission during the procedure have been identified. Moreover, the efficacy of the measures in preventing transmission have not been clearly delineated.

Methods
We identified patients with pandemic-related procedure cancellations from 3/16/2020 to 4/20/2020. Patients were stratified into tier groups (1–4) by urgency. Procedures were performed using our hospital risk mitigation strategies to minimize transmission risk. Patients who subsequently developed symptoms or tested for COVID-19 were recorded.

Results
Among patients requiring emergent procedures, 57.14% could be scheduled at their originally intended interval. COVID-19 concerns represented the most common rescheduling barrier. No patients who underwent post-procedure testing were positive for COVID-19. No cases of endoscopy staff transmission were identified.

Conclusions
Non-COVID-19 related patient care during the pandemic is a challenging process that evolved with the spread of infection, requiring dynamic monitoring and protocol optimization. We describe our successful model for reopening endoscopy suites using a tier-based system for safe reintroduction of elective procedures while minimizing transmission to patients and staff. Important barriers included financial and transmission concerns that need to be addressed to enable the return to pre-pandemic utilization of elective endoscopic procedures.
Evaluation of rehabilitation exercise effects by using gradation-based skeletal muscle echo intensity in older individuals: a one-group before-and-after trial study
Authors: Yoshiko Akito , Kaji Takashi , Kozuka Tsuyoshi , Sawazaki Takayuki , Akima Hiroshi 
Published: September 2021

Abstract
Background
Higher muscle echo intensity (EI) reflects higher content of fat and/or connective tissue within skeletal muscle, eventually inducing lower muscle strength, physical dysfunction, and metabolic impairment. Continuous exercise decreases muscle EI in older individuals; however, it is not well understood how several months’ rehabilitation exercise affects gradation-based EI. The purpose of this study was to investigate the effects of 6 months of rehabilitation exercise on gradation-based higher and lower EI in older men and women.

Methods
Twenty-seven men and women (7 men, 20 women; age, 75.6 ± 6.4 years; height, 154.3 ± 8.5 cm; weight, 55.8 ± 9.7 kg) participated in this study. This study was a one-group before-and-after trial. They needed long-term care for activities of daily living. They performed rehabilitation exercises consisting of resistance exercises using a hydraulic resistance machine, stretching, and aerobic exercises using a recumbent bicycle once or twice a week for 6 months. B-mode ultrasonographic transverse image was taken from thigh muscles, e.g., rectus femoris, vastus lateralis, and biceps femoris. We calculated gradation-based cross-sectional area (CSA) from thigh muscles by dividing 256 greyscale level to 10 different components levels (e.g., 0–24, 25–49, 50–74, …, 200–224 and 225–249 a.u.).

Results
Lowest EI (e.g., 0–24 a.u.) CSA of thigh muscle was significantly increased after the exercise (0.3 ± 0.3 to 1.0 ± 0.8 cm2; P < 0.05). Middle to higher EI (e.g., 50–74, 75–99, 100–124, 125–149, 150–174, 175–199 and 200–224 a.u.) CSAs were significantly decreased from 23.0 to 68.7% after the exercise (P < 0.05).

Conclusions
Several months’ rehabilitation exercise affected both lower and higher EI in older men and women. This result suggests that rehabilitation exercise changes muscle composition by increasing contractile muscle tissue and decreasing fat and connective tissues.
Antibody seroprevalence and rate of asymptomatic infections with SARS-CoV-2 in Austrian hospital personnel
Authors: Leister Iris , Ponocny-Seliger Elisabeth , Kollaritsch Herwig , Dungel Peter , Holzer Barbara , Grillari Johannes , Redl Heinz , Ponocny Ivo , Wilfing Claudia , Aigner Ludwig , Exner Markus , Stainer Michaela , Hackl Matthias , Hausner Thomas , Mittermayr Rainer , Schaden Wolfgang 
Published: September 2021

Abstract
Background
The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening.

Method
A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study.
Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days.

Results
Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%).
Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%).
In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)—with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3.

Conclusions
During the study period (May 11th–August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.
The potential value of plasma receptor interacting protein 3 in neonates with culture-positive late-onset sepsis
Authors: Gao Chuchu , Feng Zongtai , Wang Lixia , Zhao Xingxing , Fu Kai , Ma Shurong , Yang Zuming , Wang Sannan , Yu Shenglin 
Published: September 2021

Abstract
Background
Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS.

Methods
63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis.

Results
In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%.

Conclusions
RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.
Controlled arterial hypotension during resection of cerebral arteriovenous malformations
Authors: Riedel Katharina , Thudium Marcus , Boström Azize , Schramm Johannes , Soehle Martin 
Published: September 2021

Abstract
Background
Resection of cerebral arteriovenous malformations (AVM) is technically demanding because of size, eloquent location or diffuse nidus. Controlled arterial hypotension (CAH) could facilitate haemostasis. We performed a study to characterize the duration and degree of CAH and to investigate its association with blood loss and outcome.

Methods
We retrospectively analysed intraoperative arterial blood pressure of 56 patients that underwent AVM-resection performed by the same neurosurgeon between 2003 and 2012. Degree of CAH, AVM size, grading and neurological outcome were studied. Patients were divided into two groups, depending on whether CAH was performed (hypotension group) or not (control group).

Results
The hypotension group consisted of 28 patients, which presented with riskier to treat AVMs and a higher Spetzler-Martin grading. CAH was achieved by application of urapidil, increasing anaesthetic depth or a combination thereof. Systolic and mean arterial blood pressure were lowered to 82 ± 7 and 57 ± 7 mmHg, respectively, for a median duration of 58 min [25% percentile: 26 min.; 75% percentile: 107 min]. In the hypotension group, duration of surgery (4.4 ± 1.3 h) was significantly (p <  0.001) longer, and median blood loss (500 ml) was significantly (p = 0.002) higher than in the control group (3.3 ± 0.9 h and 200 ml, respectively). No case fatalities occurred. CAH was associated with a higher amount of postoperative neurological deficits.

Conclusions
Whether CAH caused neurological deficits or prevented worse outcomes could be clarified by a prospective randomised study, which is regarded as ethically problematic in the context of bleeding. CAH should only be used after strict indication and should be applied as mild and short as possible.