bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges to implementing artificial intelligence in healthcare: a qualitative interview study with healthcare leaders in Sweden
Authors: Petersson Lena , Larsson Ingrid , Nygren Jens M. , Nilsen Per , Neher Margit , Reed Julie E. , Tyskbo Daniel , Svedberg Petra
Published: July 2022

Background

Artificial intelligence (AI) for healthcare presents potential solutions to some of the challenges faced by health systems around the world. However, it is well established in implementation and innovation research that novel technologies are often resisted by healthcare leaders, which contributes to their slow and variable uptake. Although research on various stakeholders’ perspectives on AI implementation has been undertaken, very few studies have investigated leaders’ perspectives on the issue of AI implementation in healthcare. It is essential to understand the perspectives of healthcare leaders, because they have a key role in the implementation process of new technologies in healthcare. The aim of this study was to explore challenges perceived by leaders in a regional Swedish healthcare setting concerning the implementation of AI in healthcare.

Methods

The study takes an explorative qualitative approach. Individual, semi-structured interviews were conducted from October 2020 to May 2021 with 26 healthcare leaders. The analysis was performed using qualitative content analysis, with an inductive approach.

Results

The analysis yielded three categories, representing three types of challenge perceived to be linked with the implementation of AI in healthcare: 1) Conditions external to the healthcare system; 2) Capacity for strategic change management; 3) Transformation of healthcare professions and healthcare practice.

Conclusions

In conclusion, healthcare leaders highlighted several implementation challenges in relation to AI within and beyond the healthcare system in general and their organisations in particular. The challenges comprised conditions external to the healthcare system, internal capacity for strategic change management, along with transformation of healthcare professions and healthcare practice. The results point to the need to develop implementation strategies across healthcare organisations to address challenges to AI-specific capacity building. Laws and policies are needed to regulate the design and execution of effective AI implementation strategies. There is a need to invest time and resources in implementation processes, with collaboration across healthcare, county councils, and industry partnerships.
Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance
Authors: Conroy Andrea L. , Hawkes Michael T. , Leligdowicz Aleksandra , Mufumba Ivan , Starr Michelle C. , Zhong Kathleen , Namasopo Sophie , John Chandy C. , Opoka Robert O. , Kain Kevin C.
Published: July 2022

Background

Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood.

Methods

A prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression.

Results

We evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity.

Conclusions

BWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.
Placenta-derived proteins across gestation in healthy pregnancies—a novel approach to assess placental function?
Authors: Degnes Maren-Helene Langeland , Westerberg Ane Cecilie , Zucknick Manuela , Powell Theresa L. , Jansson Thomas , Henriksen Tore , Roland Marie Cecilie Paasche , Michelsen Trond Melbye
Published: July 2022

Background

Placenta-derived proteins in the systemic maternal circulation are suggested as potential biomarkers for placental function. However, the identity and longitudinal patterns of such proteins are largely unknown due to the inaccessibility of the human placenta and limitations in assay technologies. We aimed to identify proteins derived from and taken up by the placenta in the maternal circulation. Furthermore, we aimed to describe the longitudinal patterns across gestation of placenta-derived proteins as well as identify placenta-derived proteins that can serve as reference curves for placental function.

Methods

We analyzed proteins in plasma samples collected in two cohorts using the Somalogic 5000-plex platform. Antecubital vein samples were collected at three time points (gestational weeks 14–16, 22–24, and 30–32) across gestation in 70 healthy pregnancies in the longitudinal STORK cohort. In the cross sectional 4-vessel cohort, blood samples were collected simultaneously from the maternal antecubital vein (AV), radial artery (RA), and uterine vein (UV) during cesarean section in 75 healthy pregnancies. Placenta-derived proteins and proteins taken up by the placenta were identified using venoarterial differences (UV-RA). Placenta-derived proteins were defined as placenta-specific by comparison to the venoarterial difference in the antecubital vein-radial artery (AV-RA). These proteins were described longitudinally based on the STORK cohort samples using a linear mixed effects model per protein. Using a machine learning algorithm, we identified placenta-derived proteins that could predict gestational age, meaning that they closely tracked gestation, and were potential read-outs of placental function.

Results

Among the nearly 5000 measured proteins, we identified 256 placenta-derived proteins and 101 proteins taken up by the placenta (FDR < 0.05). Among the 256 placenta-derived proteins released to maternal circulation, 101 proteins were defined as placenta-specific. These proteins formed two clusters with distinct developmental patterns across gestation. We identified five placenta-derived proteins that closely tracked gestational age when measured in the systemic maternal circulation, termed a “placental proteomic clock.”

Conclusions

Together, these data may serve as a first step towards a reference for the healthy placenta-derived proteome that can be measured in the systemic maternal circulation and potentially serve as biomarkers of placental function. The “placental proteomic clock” represents a novel concept that warrants further investigation. Deviations in the proteomic pattern across gestation of such proteomic clock proteins may serve as an indication of placental dysfunction.
Mutational landscape of pan-cancer patients with PIK3CA alterations in Chinese population
Authors: Huang Qingfeng , Zhou Yang , Wang Bowen , Zhao Yi , Zhang Fengxia , Ding Bowen
Published: July 2022

Purpose

To analyze the mutational landscape of pan-cancer patients with PIK3CA mutations in Chinese population in real-world.

Methods

We analyzed PIK3CA mutation status in sequencing data of cell-free DNA from plasma and genomic DNA from matched peripheral blood lymphocyte in 11,904 Chinese pan-cancer patients, and compared them with genomic data from the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Besides, concomitant genomic aberrations in PIK3CA-mutated samples were detected to investigate cancer driver genes, as well as their enriched pathways. Meanwhile, the mutations of Alpelisib targeting genes were screened and their co-alterations were analyzed according to OncoKB definition to identify the potential actionable ones.

Results

The proportion of patients with PIK3CA mutations varied among 21 types of cancer, with the top being BRCA, CESC, SCL, and UCEC. The most common PIK3CA mutation hotspots were found to be E545K, E542K and H1047R. The Chinese cohort had significantly lower frequencies of PIK3CA mutations in breast and stomach cancers, but markedly higher PIK3CA mutation frequencies in large intestine, kidney and lung cancers than the COSMIC cohort. Compared with COSMIC cohort, the mutation frequencies of Alpelisib-targeted genes in breast cancer were significantly reduced in the Chinese cohort. All PIK3CA-mutated patients had concomitant genomic aberrations. While the most common concomitant genomic alterations occurred in TP53, EGFR and FAT1, these co-mutated genes were mainly enriched in RTK/RAS pathway, PI3K pathway and P53 pathway. Moreover, 83.6% of patients carrying mutations in Alpelisib-targeted genes had at least one actionable concomitant alteration. Level 1 actionable alteration was identified in LUAD, BRCA, COAD, LUSC, READ, and STAD.

Conclusion

Compared with the Western cohort, the mutation frequency of PIK3CA in breast cancer was reduced in the Chinese cohort. RTK/RAS pathway, PI3K pathway and P53 pathway were identified as the most common co-mutation pathways, suggesting that they may potentially serve as targets for possible Alpelisib-based combination therapy.
Comprehensive characterization reveals sputum supernatant as a valuable alternative liquid biopsy for genome profiling in advanced non-small cell lung cancer
Authors: Xie Xiaohong , Wu Jianhui , Guo Bingpeng , Wang Liqiang , Deng Haiyi , Lin Xinqing , Liu Ming , Qin Yinyin , Luo Wei , Yang Yilin , Zou Xiao , Hou Ting , Xiang Jianxing , Chen Zhange , Zhou Chengzhi
Published: July 2022

Background

Sputum biopsies offer unique advantages such as non-invasiveness and convenient collection. The one investigation so far on sputum for genome profiling in advanced non-small cell lung cancer (aNSCLC) suggested promising performance. However, it remains undefined whether clinicohistologic characteristics were associated with performance and how this knowledge could help guide choice of liquid biopsy.

Methods

Targeted sequencing with a 520-gene panel was performed on prospectively collected matched tumor tissue (TIS), plasma (PLA), and sputum supernatant (SPU) from 71 aNSCLC patients (NCT05034445). Genomic alteration detection was characterized in a series of aspects and interrogated for association with 14 clinicohistologic features. Nomograms were constructed with logistic regression for predicting the liquid biopsy type with greater sensitivity.

Results

Compared with PLA, SPU showed comparable quality control metrics, mutation detection rate (SPU: 67.6%, PLA: 70.4%), concordance with tumor tissue (67.6% vs. 73.2%), and correlation with tissue-based tumor mutation burden levels (r = 0.92 vs. 0.94). For driver alterations, detection was less sensitive with SPU (50.0%) than PLA (63.5%) in the entire cohort but similarly or more sensitive in patients with centrally located lung tumors or smoking history or for altered ALK or KRAS. Two nomograms were constructed and enabled predicting the probability of superior sensitivity with SPU with moderate to borderline high accuracy.

Conclusion

In addition to demonstrating comparable performance in multiple aspects, this study is the first to propose nomograms for choosing liquid biopsy based on clinicohistologic characteristics. Future research is warranted to delineate the clinical utility of sputum for genome profiling.
TyG index is positively associated with risk of CHD and coronary atherosclerosis severity among NAFLD patients
Authors: Zhao Jianqi , Fan Hongxuan , Wang Ting , Yu Bing , Mao Shaobin , Wang Xun , Zhang Wenjing , Wang Leigang , Zhang Yao , Ren Zhaoyu , Liang Bin
Published: July 2022

Background

Insulin resistance (IR), endothelial dysfunction, inflammation, glucose and lipid metabolism disorders, and thrombosis are believed involved in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index, a new IR indicator, is correlated with NAFLD occurrence and severity, but its relationship with CHD risk remains unclear. This study investigated the correlation between TyG index and CHD risk among NAFLD patients.

Methods

This cross-sectional study included 424 patients with NAFLD and chest pain in the Department of Cardiology, The Second Hospital of Shanxi Medical University, from January 2021 to December 2021. The TyG index was calculated and coronary angiography performed. All individuals were divided into NAFLD + CHD and NAFLD groups and then by TyG index level. The t-test, Mann–Whitney U-test, or one-way analysis of variance compared differences in continuous variables, while the chi-square test or Fisher’s exact test compared differences in categorical variables. Logistic regression analysis determined the independent protective or hazardous factors of NAFLD with CHD. The receiver operating characteristic curve evaluated the ability of different TyG index rule-in thresholds to predict CHD. The relationship between Gensini score and TyG index was evaluated using linear correlation and multiple linear regression.

Results

CHD was detected in 255 of 424 patients. Compared to NAFLD group, multivariate logistic regression showed that TyG index was a risk factor for CHD among NAFLD patients after adjustment for age, sex, hypertension, and diabetes mellitus with the highest odds ratio (OR, 2.519; 95% CI, 1.559–4.069; P < 0.001). TG, low-density lipoprotein cholesterol, FBG and TYG–body mass index were also risk factors for CHD among NAFLD patients. High-density lipoprotein cholesterol level was a protective factor for CHD events in patients with NAFLD. In an in-depth analysis, multivariate logistic regression analysis showed that each 1-unit increase in TyG index was associated with a 2.06-fold increased risk of CHD (OR, 2.06; 95% CI, 1.16–3.65; P = 0.013). The multifactor linear regression analysis showed each 0.1-unit increase in TyG in the NAFLD-CHD group was associated with a 2.44 increase in Gensini score (β = 2.44; 95% CI, 0.97–3.91; P = 0.002).

Conclusions

The TyG index was positively correlated with CHD risk in NAFLD patients and reflected coronary atherosclerosis severity.
Emerging vancomycin-non susceptible coagulase negative Staphylococci associated with skin and soft tissue infections
Authors: Akinduti Paul A. , Obafemi Yemisi Dorcas , Ugboko Harriet , El-Ashker Maged , Akinnola Olayemi , Agunsoye Chioma Jane , Oladotun Abiola , Phiri Bruno S. J. , Oranusi Solomon U.
Published: July 2022

Backgrounds

Observable emergence of Vancomycin-Non susceptible Coagulase-negative Staphylococci (VNS-CoNS) associated with skin and soft tissue infections spreading among the urban and rural populace is gradually intensifying severe complications. The isolated VNS-CoNS were evaluated with Matrix-assisted Laser Desorption/ionization Time of Flight Mass Spectrometry (MALDI ToF MS) for species characterization and pan-antimicrobial resistance pattern.

Methods

Out of 256 clinical samples collected including pus, abscess, ear swabs, eye swabs, and aspirates, 91 CoNS isolates were biotyped and further characterized with MALDI-TOF MS. Staphylococci marker genes, Vancomycin susceptibility, and biofilm assays were performed.

Results

Of 91 CoNS isolates, S.cohnii (2.3%), S.condimentii (3.4%), S. saprophyticus (6.7%), and S.scuri (21.1%) were characterized with MALDI-TOF with significant detection rate (99.4%; CI 95, 0.775–0.997, positive predictive values, 90.2%) compared to lower biotyping detection rate (p = 0.001). Hemolytic VNS-CoNS lacked nuc, pvl and spa genes from wound, ear, and aspirates of more 0.83 MARI clustered into a separate phylo-diverse group and were widely distributed in urban and peri-urban locations. MALDI TOF–MS yielded a high discriminatory potential of AUC-ROC score of 0.963 with true-positivity prediction. VNS-CoNS of MIC ≥ 16 µg/mL were observed among all the ages with significant resistance at 25th and 75th quartiles. More than 10.5% of CoNS expressed multi-antibiotic resistance with more than 8 µg/mL vancomycin cut-off values (p < 0.05).

Conclusion

Antibiotic resistant CoNS should be considered significant pathogens rather than contaminant. Biofilm producing VNS-S. sciuri and S. condimentii are potential strains with high pathological tropism for skin, soft tissues and wound infections, and these strains require urgent surveillance in peri-urban and rural communities.
Effects of body mass index and serum albumin on overall survival in patients with cancer undergoing pancreaticoduodenectomy: a single-center retrospective cohort study
Authors: Cui Lei , Yu Huiping , Sun Qingmei , Miao Yi , Jiang Kuirong , Fang Xiaoping
Published: July 2022

Objectives

We aimed to explore whether body mass index (BMI) and albumin were associated with overall survival (OS) in individuals who underwent pancreaticoduodenectomy (PD) for cancer.

Methods

Three-hundred twenty-nine consecutive patients who underwent PD for cancer were enrolled from January 2020 to December 2020. All clinicopathological information was extracted based on medical records. The survival follow-ups were regularly performed and ended on June 30, 2021. The Kaplan-Meier survival analysis and univariate and multivariate Cox proportional-hazards models were used to assess the association of BMI and albumin with OS.

Results

Of the 329 patients, 186 (56.5%) were male, and median age at admission was 65.0 (56.0–71.0) years. There were 258 patients (78.4%) with BMI < 25.0 kg/m2 and 89 patients (27.05%) with albumin < 35.0 g/L respectively. In overall cohort, BMI < 25.0 kg/m2 was associated with OS (adjusted HR = 3.516, 95% CI = 1.076–11.492, P = 0.037). In contrast, albumin < 35.0 g/L did not affect OS. Subgroup analysis showed, in patients with pancreas lesion, BMI < 25.0 kg/m2 had a higher risk for OS compared to BMI ≥ 25.0 kg/m2 (adjusted HR = 3.209, 95% CI = 0.985–10.451, P = 0.048), while albumin < 35.0 g/L was not linked to OS. In patients with lesion in ampulla of Vater, duodenum, or common bile duct, there was no significant association of BMI and albumin with OS.

Conclusions

BMI, rather than serum albumin, was associated with OS in patients who underwent PD for cancer.
Population pharmacokinetic modeling of CSF to blood clearance: prospective tracer study of 161 patients under work-up for CSF disorders
Authors: Hovd Markus Herberg , Mariussen Espen , Uggerud Hilde , Lashkarivand Aslan , Christensen Hege , Ringstad Geir , Eide Per Kristian
Published: July 2022

Background

Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases.

Methods

Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references.

Results

Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles.

Conclusions

The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.
The effects of lumbar fusion and non-fusion surgery on the development of Modic changes
Authors: Mu Xiaoping , Kim Seong Woong , Uhl Eberhard , Schöller Karsten
Published: July 2022

Background

The aim of this study was to investigate the influence of lumbar fusion and non-fusion surgery on the postoperative development of Modic changes (MCs).

Methods

A total of 270 patients who underwent lumbar fusion, microsequestrectomy, microdiscectomy, and microdecompression, and who were examined by pre- and postoperative magnetic resonance imaging during the period of January 2012 to December 2018, were included in this retrospective study. The incidence of new postoperative MCs and the change of volume of preexisting MCs after surgery were investigated.

Results

The total incidence of new MCs following lumbar surgical procedures was 36.3%. Lumbar fusion showed a tendency towards a lower postoperative incidence of new MCs than the other three lumbar surgical procedures. The first postoperative year seems to be the most active phase for the development of new MCs. The postoperative volumes of MCs in patients who underwent lumbar non-fusion procedures were significantly greater than those before surgery (P < 0.01). However, no significant difference was detected between pre- and postoperative volumes of MCs in patients with lumbar fusion (P > 0.05).

Conclusion

Lumbar surgical procedures contribute to the development of new MCs, particularly non-fusion surgeries. However, further studies are needed to confirm the clinical relevance of these findings.
Aberrant miR-874-3p/leptin/EGFR/c-Myc signaling contributes to nasopharyngeal carcinoma pathogenesis
Authors: Luo Sheng-Dean , Tsai Hsin-Ting , Hwang Chung-Feng , Chiu Tai‐Jan , Li Shau‐Hsuan , Hsu Ya-Ling , Hsiao Chang-Chun , Chen Chang-Han
Published: July 2022

Background

Leptin is important in physiological and pathological functions in various cancers, however, the significance and mechanisms of leptin in nasopharyngeal carcinoma remain ambiguous.

Methods

Leptin expression was analyzed by QPCR, immunohistochemistry, Western blotting, and TCGA database. The impact of gain- or loss-of-function of leptin were determined by MTT, colony formation, wound healing, and Transwell assays in NPC cells, and by a xenograft tumor model. Leptin-modulated glucose consumption and lactate production were assessed by ELISA. Furthermore, leptin-regulated signaling pathways were examined by QPCR and Western blotting assays. The immunoprecipitation assay was conducted to determine interaction between leptin and EGFR. In addition, miR-874-3p-regulated leptin expression was evaluated using bioinformatics, QPCR, luciferase assay, AGO2-RIP assay, and Western blotting.

Results

In this study, we found that leptin was highly expressed in the sera and tumor tissues of patients with NPC, and elevated leptin expression was associated with advanced clinical features and poor prognosis. Functional assays demonstrated that leptin remarkably promoted NPC cell growth, motility, and glycolysis in vitro and in vivo. Mechanistically, leptin associated with EGFR, resulting in enhanced cell growth through the regulation of cell-cycle related markers, glycolysis-related genes, and EGFR/AKT/c-Myc signaling. Moreover, leptin potentiated the invasive capacity of NPC cells by promoting EMT. We further explored that miR-874-3p influenced leptin-mediated NPC progression. Overexpression of miR-874-3p prevented cell growth, motility, glucose consumption, and lactate production in NPC cells, whereas miR-874-3p inhibition had the opposite effects. AGO-RIP assays confirmed that Argonaute 2 (AGO2), a protein associated with miR-874-3p, regulated leptin expression in NPC cells. The rescue assays indicated that inhibition of leptin suppressed the effects of miR-874-3p inhibitor. In clinical specimens, miR-874-3p was negatively correlated with leptin.

Conclusions

Leptin may serve as a novel prognostic factor and potential therapeutic target for patients with NPC. In addition, a newly discovered regulatory axis of leptin/EGFR/AKT/c-Myc can provide a novel therapeutic strategy for NPC.
Retraction Note: The significance of the change pattern of serum CA125 level for judging prognosis and diagnosing recurrences of epithelial ovarian cancer
Authors: Yang Zhi-jun , Zhao Bing-bing , Li Li
Published: July 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13048-016-0266-3.
SwinOCSR: end-to-end optical chemical structure recognition using a Swin Transformer
Authors: Xu Zhanpeng , Li Jianhua , Yang Zhaopeng , Li Shiliang , Li Honglin
Published: July 2022

Optical chemical structure recognition from scientific publications is essential for rediscovering a chemical structure. It is an extremely challenging problem, and current rule-based and deep-learning methods cannot achieve satisfactory recognition rates. Herein, we propose SwinOCSR, an end-to-end model based on a Swin Transformer. This model uses the Swin Transformer as the backbone to extract image features and introduces Transformer models to convert chemical information from publications into DeepSMILES. A novel chemical structure dataset was constructed to train and verify our method. Our proposed Swin Transformer-based model was extensively tested against the backbone of existing publicly available deep learning methods. The experimental results show that our model significantly outperforms the compared methods, demonstrating the model’s effectiveness. Moreover, we used a focal loss to address the token imbalance problem in the text representation of the chemical structure diagram, and our model achieved an accuracy of 98.58%.
Regulation and dysregulation of hair regeneration: aiming for clinical application
Authors: Yue Zhicao , Yang Fang , Zhang Jianglin , Li Ji , Chuong Cheng-Ming
Published: July 2022

Hair growth and regeneration represents a remarkable example of stem cell function. Recent progress emphasizes the micro- and macro- environment that controls the regeneration process. There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration, which include local growth factors, immune and neuroendocrine signals, and dietary and environmental factors. This is better suited for clinical application in multiple forms of hair disorders: in male pattern hair loss, the stem cells are largely preserved, but androgen signaling diminishes hair growth; in alopecia areata, an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability. Genome-wide association studies further revealed the genetic bases of these disorders, although the precise pathological mechanisms of the identified loci remain largely unknown. By analyzing the dysregulation of hair regeneration under pathological conditions, we can better address the complex interactions among stem cells, the differentiated progeny, and mesenchymal components, and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration. The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.
Immunotherapy for people with clinically isolated syndrome or relapsing-remitting multiple sclerosis: treatment response by demographic, clinical, and biomarker subgroups (PROMISE)—a systematic review protocol
Authors: Lehnert Thomas , Röver Christian , Köpke Sascha , Rio Jordi , Chard Declan , Fittipaldo Andrea V. , Friede Tim , Heesen Christoph , Rahn Anne C.
Published: July 2022

Background

Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system with an increasing worldwide prevalence. Since 1993, more than 15 disease-modifying immunotherapies (DMTs) have been licenced and have shown moderate efficacy in clinical trials. Based on the heterogeneity of the disease and the partial effectiveness of therapies, a personalised medicine approach would be valuable taking individual prognosis and suitability of a chosen therapy into account to gain the best possible treatment effect.

The primary objective of this review is to assess the differential treatment effects of all approved DMTs in subgroups of adults with clinically isolated syndrome or relapsing forms of MS. We will analyse possible treatment effect modifiers (TEM) defined by baseline demographic characteristics (gender, age), and diagnostic (i.e. MRI measures) and clinical (i.e. relapses, disability level) measures of MS disease activity.

Methods

We will include all published and accessible unpublished primary and secondary analyses of randomised controlled trials (RCTs) with a follow-up of at least 12 months investigating the efficacy of at least one approved DMT, with placebo or other approved DMTs as control intervention(s) in subgroups of trial participants. As the primary outcome, we will address disability as defined by the Expanded Disability Status Scale or multiple sclerosis functional composite scores followed by relapse frequency, quality of life measures, and side effects. MRI data will be analysed as secondary outcomes.

MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL and major trial registers will be searched for suitable studies. Titles and abstracts and full texts will be screened by two persons independently using Covidence. The risk of bias will be analysed based on the Cochrane “Risk of Bias 2” tool, and the certainty of evidence will be assessed using GRADE.

Treatment effects will be reported as rate ratio or odds ratio. Primary analyses will follow the intention-to-treat principle. Meta-analyses will be carried out using random-effects models.

Discussion

Given that individual patient data from clinical studies are often not available, the review will allow to analyse the evidence on TEM in MS immunotherapy and thus support clinical decision making in individual cases.

Systematic review registration

PROSPERO CRD42021279665.
Maternal interpersonal problems and attachment security in adolescent offspring
Authors: Kerr Sophie , Penner Francesca , Ilagan Gabrielle , Choi-Kain Lois , Sharp Carla
Published: July 2022

Background

Research on parent-level factors linked to adolescent attachment security would inform interventions to prevent or reduce youth psychopathology and other negative outcomes. The current study examined one relevant parent-level variable: maternal interpersonal problems. Interpersonal problems, a key characteristic of personality pathology, are well described by the interpersonal circumplex (IPC) and have been shown to be associated with maladaptive adult attachment in close/romantic relationships; however, studies have not examined relationships with offspring attachment. Therefore, the first aim of the current study was to examine the relationship between maternal interpersonal problems and adolescent attachment insecurity. Based on previous evidence that parents’ recalled bonding with caregivers is associated with the quality of bonding and attachment with offspring, the second aim was to examine whether mothers’ recalled bonding with their own mothers partially explained this relationship.

Methods

Participants included 351 psychiatric inpatient adolescents (Mage = 15.26, 64.1% female) and their biological mothers. Logistic regressions tested whether maternal interpersonal problems were associated with Child Attachment Interview classifications (secure vs. insecure; secure vs. preoccupied vs. dismissing; not disorganized vs. disorganized). A mediation model (N = 210) tested whether the relationship between maternal interpersonal problems and adolescent attachment was mediated by the mother’s recalled maternal bonding.

Results

Maternal interpersonal problems were associated with insecure (vs. secure), dismissing (vs. secure), and preoccupied (vs. secure) attachment. There was no significant relationship between maternal interpersonal problems and disorganized attachment. Mediation analyses showed that maternal interpersonal problems were indirectly related to adolescent attachment security via the mother’s recalled maternal care, though only a small amount of variance (7%) in adolescent offspring attachment was accounted for by the model.

Conclusions

Results provide the first evidence that maternal interpersonal problems are associated with higher likelihood of insecure attachment in adolescents. Therefore, researchers could consider drawing upon the IPC literature to further examine mechanisms of intergenerational risk and to tailor interventions aimed to improve parent-child relations and attachment. Additionally, findings highlight the mediating role of the mothers’ recalled experiences with caregivers in the transmission of risk, suggesting attachment-based or mentalization-based interventions may be helpful for mothers with interpersonal problems and personality pathology.
Dynamic characteristics of built heritage using ambient noise recordings
Authors: Hemeda Sayed
Published: July 2022

The paper addresses the investigation of the dynamic characteristics of a case study, the Egyptian church of Abu serga. To this aim some in situ investigations have been conducted and related results are discussed. The paper presents interesting and innovative aspects, mainly related to the characteristics of the church investigated, covering a lack of knowledge in the scientific literature due to the typology of the church. The integrated geotechnical and geophysical investigation techniques assessed the level of seismic and other geo-environmental risks that Abu serga church suffers from. It suffers multiple Geo-environmental hazards. The main objectives of this pilot study are as follows: (1) Identifying the shear velocity Vs analysis profile of the subsoil and also the resonant frequency of soil and the historical building of Abu serga church using ambient noise recordings (microtremors) to assess the level of seismic and other geo-environmental hazards. (2) Understanding the damage to the historic building caused by the recent earthquakes. (3) Offering technical support and advice on intervention retrofitting for the historic damaged structure.

In this study, ambient noise recordings have been processed through horizontal to vertical spectral ratios to examine the main frequencies and to examine whether the building has its main frequency close to that of the soil in order to identify potential resonance phenomena. Numerous ambient noise recordings were recorded on the soil, in the basement, and at each floor of the buildings.

This study suggests moderate level of earthquake activity at Abu serga church and is in a good agreement with the fact that “Egypt is a part of the stable African Shield”, but the existence of old structures such as the Abu serga church may reduce the ability to resist any earthquake shaking.
Tourniquet use in total knee arthroplasty and the risk of infection: a meta-analysis of randomised controlled trials
Authors: Magan A. A. , Dunseath O. , Armonis P. , Fontalis A. , Kayani B. , Haddad F. S.
Published: July 2022

Purpose

The intra-operative use of tourniquets during Total Knee Arthroplasty (TKA) is common practice. The advantages of tourniquet use include decreased operating time and the creation of a bloodless visualisation field. However, tourniquet use has recently been linked with increased post-operative pain, reduced range of motion, and slower functional recovery. Importantly, there is limited evidence of the effect of tourniquet use on infection risk. The purpose of this systematic review and meta-analysis is to fill this gap in the literature by synthesising data pertaining to the association between tourniquet use and infection risk in TKA.

Methods

A systematic literature search was performed on Pubmed, Embase, Cochrane and clinicaltrials.gov up to May 2021. Randomized control trials were included, comparing TKA outcomes with and without tourniquet use. The primary outcome was overall infection rate. Secondary outcomes included superficial and deep infection, skin necrosis, skin blistering, DVT rate, and transfusion rate.

Results

14 RCTs with 1329 patients were included. The pooled incidence of infection in the tourniquet group (4.0%, 95% CI = 2.7–5.4) was significantly higher compared to the non-tourniquet group (2.0%, 95% CI = 1.1–3.1) with an OR of 1.9 (95% CI = 1.1–3.76, p = 0.03). The length of hospital stay, haemoglobin drop (0.33 95% CI =0.12–0.54), P = 0.002) and transfusion rates (OR of 2.7, 95%CI = 1.4–5.3, P = < 0.01) were higher in the tourniquet group than the non-tourniquet group. The difference in the length of inhospital stay was 0.24 days favouring the non-tourniquet group (95% CI = 0.10–0.38, P = < 0.01). The incidence of skin blistering (OR 2.6, 95% CI = 0.7–9.9, p = 0.17), skin necrosis (OR 3.0, 95% CI = 0.50–19.3, p = 0.25), and DVT rates (OR 1.5, 95% CI = 0.60–3.60, p = 0.36) did not differ between the two groups.

Conclusion

Quantitative synthesis of the data suggested tourniquet use was associated with an increased overall risk of infection, intraoperative blood loss, need for blood transfusion and longer hospital stay. Findings of this meta-analysis do not support the routine use of tourniquet in TKA and arthroplasty surgeons should consider any potential additional risks associated with its use.

Level of evidence

meta-analysis, Level II.
Developing an intrauterine device self-removal guide: a mixed methods qualitative and small pilot study
Authors: Collins Francesca , Gilmore Kelly , Petrie Kelsey A. , Benson Lyndsey S.
Published: July 2022

Background

The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception (LARC) with few contraindications. Users, however, often encounter barriers to desired removal. IUD self-removal may mitigate these obstacles. We sought to develop a guide for IUD self-removal with the aim of increasing user control over the method.

Methods

This was a two-phase mixed-methods qualitative and small pilot study with the aim of developing an IUD self-removal guide. We conducted an online content analysis of advice for IUD self-removal as well as interviews with expert key informants to develop an IUD self-removal guide. We next recruited IUD-users who had previously attempted self-removal to participate in focus group discussion and individual interviews to further refine the guide. In the second phase of the study, we piloted the guide among eight IUD-users seeking removal interested in attempting self-removal.

Results

Expert key informants agreed that IUD self-removal was safe and low risk. The primary components of successful IUD self-removal elicited were ability to feel and grasp the strings, a crouched down position, and multiple attempts. A preference for presenting IUD self-removal as safe was emphasized. In the second phase, participants in the clinical pilot suggested more information for non-palpable strings, but liked the style and information provided. One participant successfully removed their IUD.

Conclusions

IUD-users reported satisfaction with our guide. In our small pilot, the majority were unable to remove their own IUD. A larger study is needed to assess acceptability, feasibility, and efficacy in increasing successful self-removal.
A rare case of left inferior vena cava presenting with May-Thurner syndrome
Authors: Moosavi Jamal , Sadeghipour Parham , Mohebbi Bahram , Rezaei-Kalantari Kiara , Khalilipur Ehsan
Published: July 2022

Background

May–Thurner anomaly is characterized as external venous compression by the arterial framework against hard bony structures. This chronic anatomical lesion infrequently leads to deep vein thrombosis in the lower extremity, and it may lead to leg swelling as a long-term post-thrombotic complication. Left iliac vein compression may not be as uncommon as was previously thought, and it typically occurs in women more than men. Congenital anomalies of venous tree are not rare; they exist in 8.7% of the general population.

Case-presentation

We herein present the first case of right-sided May Thurner Syndrome in a patient with IVC anomalies. In our patient, both common iliac veins formed the left-sided IVC, which extended to the hemiazygos vein and the superior vena cava. Additionally, there was a right-sided suprarenal IVC, which extended to the right atrium.

Conclusion

Understanding the proper anatomy in May-Thurner syndrome helps in better decision making for management of disease pathophysiology.
Clinical and laboratory evaluation of sicca complaints: distinctive aspects of primary, secondary and non-Sjogren syndrome
Authors: de Oliveira Fabíola Reis , Motta Ana Carolina F. , Módulo Carolina Maria , Garcia Denny Marcos , Chiorini John A. , Louzada-Junior Paulo , Rocha Eduardo Melani
Published: July 2022

Background

Sjögren Syndrome (SS) is a systemic autoimmune disease with a wide spectrum of manifestations that can lead to misdiagnosis. This study describes and compares demographic, clinical, serological, and histopathological data from subjects with SS and non-Sjögren Syndrome (NSS). It also details specific features within the primary SS (pSS) and secondary SS (sSS) groups identifying sub-groups.

Methods

The sample included individuals referred to an academic medical center in Brazil for investigation of SS from 2012 to 2020. Patients were retrospectively classified as primary SS (pSS), secondary SS (sSS), or NSS, based on the American-European Consensus Group criteria (AECG-2002), after multi-professional clinical and laboratory evaluation.

Results

A total of 676 individuals were screened and 510 (75.4%) completed the assessments; 198 patients were classified as pSS, 149 as sSS, and 163 as NSS. Symptoms and glandular dysfunction tests were similar in the groups. Concerning pSS, extraglandular manifestations were present in 59% of patients; the elderly had more dry symptoms and peripheral neurological disorders; and 2.5% developed non-Hodgkin lymphoma. In sSS, each overlap promoted distinct clinical and laboratory variants. Several alternative diagnoses were identified as a cause of sicca complex in NSS group.

Conclusions

The diagnosis of SS remains a challenge behind dryness. Up to 31% of the suspected cases had other conditions associated to the symptoms. Histopathological analysis of LSG and SSa determined the diagnostic. Aging in pSS and overlap disease in sSS were responsible for distinct phenotypes and characteristic sub-groups in SS.
Role of animal models in biomedical research: a review
Authors: Mukherjee P. , Roy S. , Ghosh D. , Nandi S. K.
Published: July 2022

The animal model deals with the species other than the human, as it can imitate the disease progression, its’ diagnosis as well as a treatment similar to human. Discovery of a drug and/or component, equipment, their toxicological studies, dose, side effects are in vivo studied for future use in humans considering its’ ethical issues. Here lies the importance of the animal model for its enormous use in biomedical research. Animal models have many facets that mimic various disease conditions in humans like systemic autoimmune diseases, rheumatoid arthritis, epilepsy, Alzheimer’s disease, cardiovascular diseases, Atherosclerosis, diabetes, etc., and many more. Besides, the model has tremendous importance in drug development, development of medical devices, tissue engineering, wound healing, and bone and cartilage regeneration studies, as a model in vascular surgeries as well as the model for vertebral disc regeneration surgery. Though, all the models have some advantages as well as challenges, but, present review has emphasized the importance of various small and large animal models in pharmaceutical drug development, transgenic animal models, models for medical device developments, studies for various human diseases, bone and cartilage regeneration model, diabetic and burn wound model as well as surgical models like vascular surgeries and surgeries for intervertebral disc degeneration considering all the ethical issues of that specific animal model. Despite, the process of using the animal model has facilitated researchers to carry out the researches that would have been impossible to accomplish in human considering the ethical prohibitions.
Structural damage detection from dynamic responses of the bridge deck under a moving load using discrete wavelet transform
Authors: Gavgani Seyyed Ali Mousavi , Zarnaghi Amir Ahmadnejad , Heydari Sajad
Published: July 2022

Early detection of structural damages and making necessary interventions to repair them are one of the main challenges in structural health monitoring. The wavelet transform is one of the common methods for this purpose, and its efficiency is proven by many researchers. In the present study, this approach is used to assess the performance of Sani-khani bridge with single and multiple-damage scenarios. For this purpose, the displacement response difference between the intact and damaged bridge decks under a moving load is analyzed by discrete wavelet transform (DWT). In the present study, 10 sensors and one-time sampling are used, In fact, the proposition of a method that uses the minimum number of required sensors for practical damage detection. To verify the reliability of the suggested method, not only different damage locations were considered, but also 5% noise is considered for the input signals. The attained results proved that even in the presence of the noise, the proposed approach can detect the damage locations with acceptable accuracy. The accuracy of the method for middle and side damages is higher than corner damages.