bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative polyadenylation dysregulation contributes to the differentiation block of acute myeloid leukemia
Authors: Davis Amanda G. , Johnson Daniel T. , Zheng Dinghai , Wang Ruijia , Jayne Nathan D. , Liu Mengdan , Shin Jihae , Wang Luyang , Stoner Samuel A. , Zhou Jie-Hua , Ball Edward D. , Tian Bin , Zhang Dong-Er
Published: September 2021

Posttranscriptional regulation has emerged as a driver for leukemia development and an avenue for therapeutic targeting. Among posttranscriptional processes, alternative polyadenylation (APA) is globally dysregulated across cancer types. However, limited studies have focused on the prevalence and role of APA in myeloid leukemia. Furthermore, it is poorly understood how altered poly(A) site usage of individual genes contributes to malignancy or whether targeting global APA patterns might alter oncogenic potential. In this study, we examined global APA dysregulation in patients with acute myeloid leukemia (AML) by performing 3' region extraction and deep sequencing (3'READS) on a subset of AML patient samples along with healthy hematopoietic stem and progenitor cells (HSPCs) and by analyzing publicly available data from a broad AML patient cohort. We show that patient cells exhibit global 3' untranslated region (UTR) shortening and coding sequence lengthening due to differences in poly(A) site (PAS) usage. Among APA regulators, expression of FIP1L1, one of the core cleavage and polyadenylation factors, correlated with the degree of APA dysregulation in our 3'READS data set. Targeting global APA by FIP1L1 knockdown reversed the global trends seen in patients. Importantly, FIP1L1 knockdown induced differentiation of t(8;21) cells by promoting 3'UTR lengthening and downregulation of the fusion oncoprotein AML1-ETO. In non-t(8;21) cells, FIP1L1 knockdown also promoted differentiation by attenuating mechanistic target of rapamycin complex 1 (mTORC1) signaling and reducing MYC protein levels. Our study provides mechanistic insights into the role of APA in AML pathogenesis and indicates that targeting global APA patterns can overcome the differentiation block in patients with AML.
Nonclassical manifestations of acute GVHD
Authors: Zeiser Robert , Teshima Takanori
Published: September 2021

Acute graft-versus-host disease (GVHD) is a major life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). The classical target organs of acute GVHD include the intestines, liver, and skin. The damage of these organs is relatively easy to detect for the clinician as diarrhea, increased bilirubin, and rash. However, there is increasing evidence that other organs, where the acute damage is less apparent or more difficult to distinguish from drug toxicity, such as the central nervous system, lungs, ovaries and testis, thymus, bone marrow, and kidney, can be target organs of acute GVHD. Here, we review current evidence for nonclassical manifestations of acute GVHD in rodent models and in patients and discuss them in the context of novel emerging therapies for GVHD. A better understanding of the involvement of nonclassical GVHD target organs may help to improve patient outcomes after allo-HCT.
Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond
Authors: Gavriilaki Eleni , de Latour Régis Peffault , Risitano Antonio Maria
Published: September 2021

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

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

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

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

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

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

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

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

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

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.
Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China
Authors: Shafeng Nilupaer , Han Deng-feng , Ma Yun-fang , Abudusalamu Rena , Ayitimuhan Binuer
Published: September 2021

Background

The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China.

Methods

We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test.

Results

We found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found.

Conclusions

In northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.
Antipsychotics withdrawal in adults with intellectual disability and challenging behaviour: study protocol for a multicentre double-blind placebo-controlled randomised trial
Authors: Beumer Sylvie , Hamers Pauline , Oppewal Alyt , Maes-Festen Dederieke
Published: September 2021

Background

In people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour.

Methods

To investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure.

Discussion

In order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand.

Trial registration

This trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 (www.trialregister.nl).
The individual, place, and wellbeing – a network analysis
Authors: McElroy Eoin , Ashton Mathew , Bagnall Anne Marie , Comerford Terence , McKeown Mick , Patalay Praveetha , Pennington Andy , South Jane , Wilson Tim , Corcoran Rhiannon
Published: September 2021

Background

Previous research has examined individual-level and place characteristics as correlates of subjective wellbeing, with many studies concluding that individual factors (e.g. health, finances) are more strongly related to wellbeing. However, this ‘dualistic’ approach has been challenged, with some arguing that it is impossible to disentangle the effects of the two domains, and that wellbeing should be considered as part of a network of mutually reinforcing relationships between individual, community and place characteristics. We used network analysis to explore these complex associations.

Methods

Data were from a large sample of adults from a socioeconomically disadvantaged region of the United Kingdom (N = 4319). Wellbeing was assessed using the 7-item version of the Warwick–Edinburgh Mental Wellbeing Scale (SWEMWBS). Mixed graphical networks were estimated including wellbeing, place and individual-characteristic variables as nodes.

Results

We found a densely connected network in which wellbeing was associated, both directly and indirectly, with all of the individual, community and place characteristics assessed. Wellbeing was most strongly connected with individual characteristics, in particular financial difficulty and subjective physical health. However, controlling for all other variables in the network model, wellbeing was positively associated with local greenspace usage, civic agency, and neighbourhood cohesion, and negatively associated with housing disrepair. Greater specificity in these associations was observed when the wellbeing construct was broken down into its constituent parts.

Conclusions

These findings highlight the complex relationships that exist between individual, community and place characteristics in the context of subjective wellbeing, and that all domains need to be considered when developing population-level strategies to improve wellbeing. Further consideration needs to be given to how this might happen in practice, for example through a combination of consistent use of community engagement methodologies alongside Health in All Policy (HiAP) approaches.
Analyzing the reach of public health campaigns based on multidimensional aspects: the case of the syphilis epidemic in Brazil
Authors: de Morais Pinto Rafael , de Medeiros Valentim Ricardo Alexsandro , Fernandes da Silva Lyrene , Góis Farias de Moura Santos Lima Thaísa , Kumar Vivekanandan , Pereira de Oliveira Carlos Alberto , Martins Gomes de Gusmão Cristine , de Paiva Jailton Carlos , de Andrade Ion
Published: September 2021

Background

Public health campaigns aim to promote awareness, increase knowledge, and encourage a target population to adopt desirable attitudes and behaviors. Assessing their reach from a multidimensional perspective through information technology can facilitate the development of more effective campaigns in public health response.

Methods

We scrutinized seven data sources from different perspectives to assess a health campaign launched in Brazil named “Syphilis No!”. This campaign is part of an Agenda for strategic actions to reduce syphilis in Brazil which includes dissemination of educommunication materials to remind people of the importance of syphilis prevention, emphasizing “test, treat and cure” concept. We developed a multidimensional analysis framework and implemented an information system to process the data from a time series perspective, and assessed the effects over time, both before and after the campaign. We descriptively analyzed data related to the campaign, including e-news, search engine activity, online courses, serological tests, medication distribution and case notification rates.

Findings

Regarding search engine activity, we observed the highest volume of search during the first week of campaigns in 2018 (between November 25th and December 7th). Nevertheless, analyzing this data in a trend plot revealed sustained growth until the end of 2019. From March 2018, the amount of e-news posts related to syphilis in Brazil, indexed by Google, followed an increasing slope, with a record peak in October 2019. In addition, data showed that 12 new online courses related to syphilis disease were available on the AVASUS Platform Learning Management System (LMS), to support efforts to promote lifelong learning for health professionals, teachers, and students. These courses reached more than 22,000 students between February 2019 and September 2020. Serological test data showed that the number of tests carried out in 2019 were 375·18% more than in 2015, even accounting for population growth. Finally, starting from the middle of 2018, the syphilis case notification rates followed a decreasing curve.

Interpretation

From this perspective, the “Syphilis No!” Project was a positive influence, inducing policy to fight syphilis in Brazil by supporting the implementation of a testing, treatment, and cure agenda (#TesteTrateCure). Certainly, this inference was made by analyzing multidimensional aspects and because, prior to 2018, the country had largely neglected this disease, with no records of communication actions during that period.
Repeat abortion and associated factors among women seeking abortion services in northwestern China: a cross-sectional study
Authors: Li Chen , Gao Jianmin , Liu Jinlin
Published: September 2021

Background

Repeat abortion is a significant public health problem in China. International knowledge about repeat abortion and its associated factors in Chinese women is scarce. This study aimed to analyze the prevalence of repeat abortion among women seeking abortion services with unintended pregnancies in northwestern China and to identify factors associated with the repeat abortion from both two perspectives of abortion seekers themselves and their sexual partners.

Methods

This cross-sectional survey was conducted from May 1st to May 31st, 2020, in 90 medical institutions in Xi’an, the largest city in northwestern China. All women seeking abortions within the first 12 weeks of pregnancy were invited to participate in this survey; however, only those abortion seekers with unintended pregnancies were extracted and included in this study. Pearson’s chi-squared tests, Kolmogorov-Smirnov tests, and binary logistic regression analysis were performed.

Results

Of 3397 abortion seekers, 56.6% (1924) were undergoing repeat abortions. Participants who were older than 30 years (OR: 1.37, 95% CI: 1.08–1.73 for 31–35 years; 1.82, 1.29–2.57 for ≥36 years), received a low-level education (1.86, 1.42–2.43 for ≤senior high school; 1.46, 1.17–1.83 for junior college), were jobless (2.46, 1.18–5.13), had one child (1.54, 1.10–2.17), had a general (1.60, 1.28–1.98) or no (2.51, 2.02–3.11) cognition of possible adverse health effects of having abortions, and had used contraception at the time of conception, i.e., condoms (1.33, 1.09–1.61), withdrawal (1.43, 1.12–1.84), and emergency measures (1.48, 1.09–1.99) were more likely to undergo a repeat abortion. Besides, participants whose sexual partners were older than 30 years (1.33, 1.06–1.68 for 31–35 years; 2.13, 1.56–2.91 for ≥36 years), attained a low-level education (1.66, 1.28–2.15 for ≤senior high school; 1.38, 1.10–1.74 for junior college), received a high-level monthly income (1.34, 1.08–1.65 for ≥6001 Yuan), and had a weak or very weak willingness to use contraception (6.84, 2.42–19.33) were more likely to have a repeat abortion.

Conclusions

The study findings highlight the problem of repeat abortion in China and suggest the need for government and civil society to increase efforts to reduce the risks of unintended pregnancy and repeat abortion in China. One approach may be to offer better access to reproductive health and contraception knowledge to women and their sexual partners and to promote their correct, consistent, and effective contraception practice.
A nomogram for predicting postoperative pulmonary infection in esophageal cancer patients
Authors: Li Shuang , Su Jingwen , Sui Qiyu , Wang Gongchao
Published: September 2021

Background

Although postoperative pulmonary infection (POI) commonly occurs in patients with esophageal cancer after curative surgery, a patient-specific predictive model is still lacking. The main aim of this study is to construct and validate a nomogram for estimating the risk of POI by investigating how perioperative features contribute to POI.

Methods

This cohort study enrolled 637 patients with esophageal cancer. Perioperative information on participants was collected to develop and validate a nomogram for predicting postoperative pulmonary infection in esophageal cancer. Predictive accuracy, discriminatory capability, and clinical usefulness were evaluated by calibration curves, concordance index (C-index), and decision curve analysis (DCA).

Results

Multivariable logistic regression analysis indicated that length of stay, albumin, intraoperative bleeding, and perioperative blood transfusion were independent predictors of POI. The nomogram for assessing individual risk of POI indicated good predictive accuracy in the primary cohort (C-index, 0.802) and validation cohort (C-index, 0.763). Good consistency between predicted risk and observed actual risk was presented as the calibration curve. The nomogram for estimating POI of esophageal cancer had superior net benefit with a wide range of threshold probabilities (4–81%).

Conclusions

The present study provided a nomogram developed with perioperative features to assess the individual probability of infection may conducive to strengthen awareness of infection control and provide appropriate resources to manage patients at high risk following esophagectomy.
The influence of pelvic tilt on stress distribution in the acetabulum: finite element analysis
Authors: Hasegawa Kazuhiro , Kabata Tamon , Kajino Yoshitomo , Inoue Daisuke , Sakamoto Jiro , Tsuchiya Hiroyuki
Published: September 2021

Background

Finite element analysis (FEA) has been previously applied for the biomechanical analysis of acetabular dysplasia and osteotomy. However, until now, there have been little reports on the use of FEA to evaluate the effects of pelvic tilt on stress distribution in the acetabulum.

Methods

We used the Mechanical Finder Ver. 7.0 (RCCM, Inc., Japan) to construct finite element models based on 3D-CT data of patients, and designed dysplasia, borderline, and normal pelvic models. For analysis, body weight was placed on the sacrum and the load of the flexor muscles of the hip joint was placed on the ilium. The pelvic tilt was based on the anterior pelvic plane, and the pelvic tilt angles were -20°, 0°, and 20°. The load of the flexor muscle of the hip joint was calculated using the moment arm equation.

Results

All three models showed the highest values of von Mises stress in the -20° pelvic tilt angle, and the lowest in the 20° angle. Stress distribution concentrated in the load-bearing area. The maximum values of von Mises stress in the borderline at pelvic tilt angles of -20° was 3.5Mpa, and in the dysplasia at pelvic tilt angles of 0° was 3.1Mpa.

Conclusions

The pelvic tilt angle of -20° of the borderline model showed equal maximum values of von Mises stress than the dysplasia model of pelvic tilt angle of 0°, indicating that pelvic retroversion of -20° in borderline is a risk factor for osteoarthritis of the hip joints, similar to dysplasia.
Comparisons of different exercise interventions on glycemic control and insulin resistance in prediabetes: a network meta-analysis
Authors: Huang Li , Fang Yingjie , Tang Lijun
Published: September 2021

Background

In order to recommend the optimal type of exercise for type 2 diabetes prevention, different exercise interventions were compared with respect to their effects on glycemic control and insulin resistance.

Methods

Studies on the curative effect of aerobic exercise training (AET), resistance training (RT), or control training (CT) on prediabetes were retrieved from the PubMed, Embase, SPORTDiscus, and Cochrane Library databases. Body mass index (BMI); homeostasis model assessment of insulin resistance index (HOMA-IR); and fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and insulin levels were used as outcome indicators. The Q statistic was calculated to evaluate heterogeneity within studies. A fixed- or random-effects model was used for pooling data based on nonsignificant or significant heterogeneities. A consistency test was conducted using a node-splitting analysis.

Results

A total of 13 eligible studies were included. The results of the direct meta-analysis indicated that AET or RT could significantly reduce the HbA1c level in prediabetic individuals compared to CT [AET vs. CT: standardized mean difference (SMD) = − 0.6739, 95% confidence interval (CI) = − 0.9424 to − 0.4055 to RT vs. CT: SMD = − 1.0014, 95% CI = − 1.3582 to − 0.6446]. The findings from the network meta-analysis showed that there were no statistical differences among the four comparisons for all the indicators except for lower HbA1c level (SMD = − 0.75, 95% CI = − 1.31 to − 0.19) and HOMA-IR (SMD = − 1.03, 95% CI = − 1.96 to − 0.10) in the AET group than in the CT group. In addition, prediabetic individuals in the AET + RT group showed greater control of BMI and insulin and FBG levels than those in the other groups, whereas AET was the most effective in controlling HbA1c and HOMA-IR levels in prediabetic individuals.

Conclusion

AET, AET + RT, and RT exerted beneficial effects on insulin resistance and glycemic control in prediabetic patients. From the existing data, AET or AET + RT is preferentially recommended for these patients, although further studies may unveil RT as a promising therapy. Benefits from all types of exercise seem to occur in an intensity-dependent manner.
Teaching emergency situations during a psychiatry residency programme using a blended learning approach: a pilot study
Authors: Salles Juliette , Birmes Philippe , Schmitt Laurent , Bastiani Bruno , Soto Maria , Lafont-Rapnouil Stéphanie , Mathur Anjali , Bougon Emmanuelle , Arbus Christophe , Yrondi Antoine
Published: September 2021

Background

Emergency psychiatry is an essential component in the training of psychiatry residents who are required to make patient-centred orientation decisions. This training calls for specific knowledge as well as skills and attitudes requiring experience. Kolb introduced a theory on experiential learning which suggested that effective learners should have four types of abilities: concrete experience, reflective observation, abstract conceptualisation and active experimentation.

We aimed to evaluate a resident training programme that we designed for use in an emergency psychiatry setting based on the experimental learning theory.

Methods

We designed a four-step training programme for all first-year psychiatry residents: (i) theoretical teaching of psychiatric emergency knowledge, (ii) concrete experience of ability teaching involving an initial simulation session based on three scenarios corresponding to clinical situations frequently encountered in emergency psychiatry (suicidal crisis, hypomania and depressive episodes), (iii) reflective observation and abstract conceptualisation teaching based on videos and clinical interview commentary by a senior psychiatrist for the same three scenarios, (iv) active experimentation teaching during a second simulation session based on the same three frequently encountered clinical situations but with different scenarios.

Training-related knowledge acquisition was assessed after the second simulation session based on a multiple-choice quiz (MCQ), short-answer questions and a script concordance test (SCT). The satisfaction questionnaire was assessed after the resident had completed his/her initial session in order to evaluate the relevance of teaching in clinical practice. The descriptive analyses were described using the mean (+/- standard deviation). The comparative analyses were conducted with the Wilcoxon or Student’s t tests depending on data distribution.

Results

The residents’ mean MCQ and short-answer question scores and SCT were 7.25/10 (SD = 1.2) 8.33/10 (SD = 1.4), 77.5/100 (SD = 15.8), respectively. The satisfaction questionnaire revealed that 67 % of residents found the teaching consistent.

Conclusion

We designed a blended learning programme that associated, classical theoretical learning to acquire the basic concepts, a learning with simulation training to experiment the clinical situations and a video support to improve learning of interview skills and memory recall. The residents indicate that this training was adequate to prepare them to be on duty. However, despite this encouraging point, this program needs further studies to attest of its efficiency.