bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort
Authors: González Luis Alonso , Alarcón Graciela S. , Harvey Guillermina B , Quintana Rosana , Pons-Estel Guillermo J , Ugarte-Gil Manuel F , Vásquez Gloria , Catoggio Luis J , García Mercedes A. , Borba Eduardo F , Da Silva Nilzio A , Tavares Brenol João C , Toledano Marlene Guibert , Massardo Loreto , Neira Oscar , Pascual-Ramos Virginia , Amigo Mary-Carmen , Barile-Fabris Leonor A , De La Torre Ignacio García , Alfaro-Lozano José , Segami María I , Chacón-Díaz Rosa , Esteva-Spinetti María H , Iglesias-Gamarra Antonio , Pons-Estel Bernardo A 
Published: March 2023

Objective To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. Methods Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. Results Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43–450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02–4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01–1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91–6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. Conclusions Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.
Validation of a monoclonal unconjugated estriol antibody for use in prenatal maternal serum screening
Authors: Lambert-Messerlian Geralyn M , Bestwick Jonathan P , Wald Nicholas J 
Published: March 2023

Objectives Unconjugated estriol (uE3) is used as a marker for fetal aneuploidy in maternal serum screening tests. The goal of this study was to examine the validity of a new immunoassay for uE3 that uses a monoclonal antibody (m-uE3) rather than the more commonly used polyclonal antibody (p-uE3). Setting Assays were performed in the Special Chemistry laboratory at Women and Infants Hospital of Rhode Island. Methods Residual fresh ( n = 100) and frozen ( n = 533) second trimester serum samples from routine clinical care were tested using p-uE3 and/or m-uE3 assays. Assay results were compared between methods using Bland–Altman plots. A median equation was developed for m-uE3 results. Down syndrome risks were compared between the two assays in a case–control sample set (21 cases each matched with five controls for the completed week of gestation, duration of freezer storage and race). Results Log-transformed serum uE3 levels were highly correlated between the assays ( r = 0.93, p < 0.001), with the m-uE3 assay levels yielding, on average, 23% higher (standard deviation of differences in log uE3 concentrations = 0.07) results. Assay and gestation-based median equations were calculated and used to convert m-uE3 concentrations to multiples of the median (MoM). The m-uE3 MoM values fit a log Gaussian distribution well with a log standard deviation of 0.11. Down syndrome risk results were not significantly different between assays. Conclusions The m-uE3 assay, with results expressed in MoMs, is suitable for screening and as a monoclonal-based assay offers the advantage of a predictable and indefinite supply of antibody to perform the assay.
Clinical Experience with Drotrecogin Alfa in Treating Gram-Positive and -Negative Pathogens in Patients with Severe Sepsis
Authors: Cone Lawrence A. , Stone Richard A. , Jesser Kenneth , Nelson Richard 
Published: March 2023

Background Newer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study. Methods We treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections. Results In contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived. Conclusion Those patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.
The Novel Use of Rare Earth Magnets for the Extraction of Metallic Soft Tissue Foreign Bodies in Children
Authors: Lukish John T. , Williams Kibileri , Shah Adil , Mon Rodrigo , Lukish Jeffrey R. 
Published: March 2023

Introduction Metallic foreign bodies (mFB) are common following penetrating injuries in children. The mFB commonly occur in the head and neck region and extremity soft tissues. Removal may be indicated due to morbidity related to pain or migration. Extraction can be challenging to localize, often requiring wide exposure, and may be difficult to achieve in cosmetically sensitive areas. Different technological adjuncts have been used to facilitate foreign body removal including fluoroscopy, ultrasound, and more recently in adults, surgical magnets. The most powerful commercially available magnets are rare earth magnets comprised of neodymium iron and boron (Ndy). With the goal of reducing radiation exposure and the morbidity of mFB removal with associated soft tissue injury in children, a strategy was introduced utilizing Ndy to optimize extraction with minimal soft tissue surgical dissection. Materials and Methods Two children with extremity mFB treated with Ndy between January 2021 and July 2021 were analyzed. We utilized commercially available ring type neodymium-iron-boron magnets with dimensions of 1 3/8-inch outer diameter x 1/8-inch inner diameter and 1/16 inch thick with a power of 13 200 gauss that were processed for use according to our hospital protocols. Our main clinical indication was for the detection and retrieval of small ferromagnetic foreign bodies embedded in superficial extremity soft tissues. Results In the operating room under general anesthesia, the mFB were localized utilizing fluoroscopy. A 1.0 cm skin incision was made into the subdermal soft tissues overlying the area of the mFB. No surgical tissue dissection was performed. The mFB could not be visualized in the soft tissue. Using fluoroscopy to localize the mFB, the Ndy was then placed into the wound in close proximity to the mFB. The mFB were immediately magnetized to the Ndy and the mFB were extracted from the soft tissues without any further surgical dissection. Two simple interrupted nylon sutures were placed to close the incision. The total operative time was 2 and 2.5 minutes respectively. The children recovered uneventfully and are without complication. Conclusions The use of Ndy to remove extremity soft tissue mFB in children appears to be feasible, safe, and efficient. Use of the Ndy allowed extraction via a small incision, optimizing the aesthetic result and avoiding the need for cross-sectional imaging, extensive surgical dissection, tissue reconstruction and prolonged operative time or x-ray exposure. The development of magnets of increasing energy density may be indicated to further optimize metallic soft tissue foreign body extraction in children in a minimally invasive manner.
Previous corticosteroid exposure associates with an increased Pneumocystis jirovecii pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study
Authors: Vargas Barahona Lilian , Molina Kyle C. , Pedraza-Arévalo Laura C. , Sillau Stefan , Tagawa Alex , Scherger Sias , Chastain Daniel B. , Shapiro Leland , Tuells Jose , Franco-Paredes Carlos , Hawkins Kellie L. , Maloney James P. , Thompson George R. , Henao-Martínez Andrés F. 
Published: March 2023

Background: HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality. Objective: We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality. Methods: We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis ( n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis. Results: 1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p < 0.0001). (1→3)-β-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p < 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p < 0.001) or prednisone (49% versus 29%, p < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5–9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0–10.4, p < 0.0001) among HIV-negative patients with previous corticosteroid exposure. Conclusion: Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.
Anti-G protein antibodies targeting the RSV G protein CX3C chemokine region improve the interferon response
Authors: Bergeron Harrison C. , Kauvar Lawrence M. , Tripp Ralph A. 
Published: March 2023

Background: Respiratory syncytial virus (RSV) is a poor inducer of antiviral interferon (IFN) responses which result in incomplete immunity and RSV disease. Several RSV proteins alter antiviral responses, including the non-structural proteins (NS1, NS2) and the major viral surface proteins, that is, fusion (F) and attachment (G) proteins. The G protein modifies the host immune response to infection linked in part through a CX3 C chemokine motif. Anti-G protein monoclonal antibodies (mAbs), that is, clones 3D3 and 2D10 that target the G protein CX3C chemokine motif can neutralize RSV and inhibit G protein-CX3CR1 mediated chemotaxis. Objectives: Determine how monoclonal antibodies against the RSV F and G proteins modify the type I and III IFN responses to RSV infection. Design: As the G protein CX3 C motif is implicated in IFN antagonism, we evaluated two mAbs that block G protein CX3C-CX3CR1 interaction and compared responses to isotype mAb control using a functional cellular assay and mouse model. Methods: Mouse lung epithelial cells (MLE-15 cells) and BALB/c mice were infected with RSV Line19 F following prophylactic mAb treatment. Cell supernatant or bronchoalveolar lavage fluid (BALF) were assayed for types I and III IFNs. Cells were interrogated for changes in IFN-related gene expression. Results: Treatment with an anti-G protein mAb (3D3) resulted in improved IFN responses compared with isotype control following infection with RSV, partially independently of neutralization, and this was linked to upregulated SOCS1 expression. Conclusions: These findings show that anti-G protein antibodies improve the protective early antiviral response, which has important implications for vaccine and therapeutic design. Plain Language Summary RSV is a leading cause of respiratory disease in infants and the elderly. The only Food and Drug Administration-approved prophylactic treatment is limited to an anti-F protein monoclonal antibody (mAb), that is, palivizumab which has modest efficacy against RSV disease. Accumulating evidence suggests that targeting the RSV attachment (G) protein may provide improved protection from RSV disease. It is known that the G protein is an IFN antagonist, and IFN has been shown to be protective against RSV disease. In this study, we compared IFN responses in mouse lung epithelial (MLE-15) cells and in mice infected with RSV Line19 F treated with anti-G protein or anti-F protein mAbs. The levels of type I and III IFNs were determined. Anti-G protein mAbs improved the levels of IFNs compared with isotype-treated controls. These findings support the concept that anti-G protein mAbs mediate improved IFN responses against RSV disease, which may enable improved treatment of RSV infections.
Multi-regional COVID-19 epidemic forecast in Sweden
Authors: Xing Yihan , Gaidai Oleg 
Published: March 2023

The novel coronavirus disease 2019 (COVID-19) is a contagious disease with high transmissibility to spread worldwide, reported to present a certain burden on worldwide public health. This study aimed to determine epidemic occurrence probability at any reasonable time horizon in any region of interest by applying modern novel statistical methods directly to raw clinical data. This paper describes a novel bio-system reliability approach, particularly suitable for multi-regional health and stationary environmental systems, observed over a sufficient period of time, resulting in a reliable long-term forecast of the highly pathogenic virus outbreak probability. For this study, COVID-19 daily recorded patient numbers in most affected Sweden regions were chosen. This work aims to benchmark state-of-the-art methods, making it possible to extract necessary information from dynamically observed patient numbers while considering relevant territorial mapping. The method proposed in this paper opens up the possibility of accurately predicting epidemic outbreak probability for multi-regional biological systems. Based on their clinical survey data, the suggested methodology can be used in various public health applications. Key findings are: A novel spatiotemporal health system reliability method has been developed and applied to COVID-19 epidemic data. Accurate multi-regional epidemic occurrence prediction is made. Epidemic threshold confidence bands given.
Pathologists’ acceptance of telepathology in the Ministry of National Guard Health Affairs Hospitals in Saudi Arabia: A survey study
Authors: Alawashiz Raneem , AlDossary Sharifah Abdullah 
Published: March 2023

Introduction Evaluating users’ attitudes and acceptance of telemedicine in the early phases of implementation is critical in predicting a successful adoption and utilization of the service. Telepathology does not require a patient's presence for intercommunication; therefore, it is essential to focus on the acceptance of the main occupational groups that are involved. This study aimed to assess the attitude and acceptance of telepathology in the pathology departments of the Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia. Method A cross-sectional survey was distributed among pathologists and laboratory technologists in the pathology departments of MNGHA hospitals ( N = 78). The data collection instrument was built upon the technology acceptance model’s (TAM's) constructs of perceived usefulness (PU), perceived ease of use (PEU), attitude (ATT), and intention to use (ITU). Results In total, 64 questionnaires were completed (response rate of 82%). The acceptance levels represented by the median responses to the TAM constructs, varied from 5.5 (slightly agree) to 6 (agree). The availability of digital pathology services in the workplace was significantly correlated with the participants’ acceptance of telepathology. There was a strong correlation between ITU and PU and a moderate correlation between PEU and PU. Conclusion Results suggest that telepathology is more likely to be adopted if it is considered helpful, therefore, it is recommended to focus on its usefulness and direct benefits during the training period. The participants who were familiar with the concept of digital pathology were more receptive to using telepathology, which might emphasize the importance of introducing and familiarizing the resident with digital health during their training period.
Validation of the influence of biosignals on performance of machine learning algorithms for sleep stage classification
Authors: Choi Junggu , Kwon Seohyun , Park Sohyun , Han Sanghoon 
Published: March 2023

Background Sleep stage identification is critical in multiple areas (e.g. medicine or psychology) to diagnose sleep-related disorders. Previous studies have reported that the performance of machine learning algorithms can be changed depending on the biosignals and feature-extraction processes in sleep stage classification. Methods To compare as many conditions as possible, 414 experimental conditions were applied, considering the combination of different biosignals, biosignal length, and window length. Five biosignals in polysomnography (i.e. electrocardiogram (ECG), electroencephalogram (EEG), electromyogram (EMG), electrooculogram left, and electrooculogram right) were used to identify optimal signal combinations for classification. In addition, three different signal-length conditions and six different window-length conditions were applied. The validity of each condition was examined via classification performance from the XGBoost classifiers trained using 10-fold cross-validation. Furthermore, results considering feature importance were examined to validate the experimental results in terms of model explanation. Results The combination of EEG + EMG + ECG with a 40 s window and 120 s signal length resulted in the best classification performance (precision: 0.853, recall: 0.855, F1-score: 0.853, and accuracy: 0.853). Compared to other conditions and feature importance results, EEG signals showed a relatively higher importance for classification in the present study. Conclusion We determined the optimal biosignal and window conditions for the feature-extraction process in machine learning algorithm-based sleep stage classification. Our experimental results inform researchers in the future conduct of related studies. To generalize our results, more diverse methodologies and conditions should be applied in future studies.
Caveolin-1 is involved in fatty infiltration and bone-tendon healing of rotator cuff tear
Authors: Fang Shanhong , You Mengqiang , Wei Jie , Chen Peng 
Published: March 2023

Abstract
Background
Caveolin-1 has been predicted, based on RNA transcriptome sequencing, as a key gene in rotator cuff tear (RCT) and it is related to fatty infiltration. This study aims to elucidate the upstream and downstream mechanism of Caveolin-1 in fatty infiltration and bone-tendon healing after RCT in rat models.

Methods
Differentially expressed genes related to RCT were screened, followed by functional enrichment analysis and protein-protein interaction analysis. GATA6 was overexpressed and Caveolin-1 was knocked down in tendon stem cells (TSCs) to evaluate their effects on the adipogenic differentiation of TSCs. In addition, a RCT rat model was constructed and injected with lentivirus carrying oe-GATA6, oe-Caveolin-1 alone or in combination to assess their roles in fatty infiltration and bone-tendon healing.

Results and conclusion
Caveolin-1 was identified as a key gene involved in the RCT process. In vitro results demonstrated that Caveolin-1 knockdown inhibited adipogenic differentiation of TSCs by activating the cAMP/PKA pathway. GATA6 inhibited the transcription of Caveolin-1 and inhibited its expression, thus suppressing the adipogenic differentiation of TSCs. In vivo data confirmed that GATA6 overexpression activated the cAMP/PKA pathway by downregulating Caveolin-1 and consequently repressed fatty infiltration, promoted bone-tendon healing, improved biomechanical properties and reduced the rupture risk of injured tendon in rats after RCT. Overall, this study provides novel insights into the mechanistic action of Caveolin-1 in the fatty infiltration and bone-tendon healing after RCT.
Changes in life history parameters and transcriptome profile of Serangium japonicum associated with feeding on natural prey (Bemisia tabaci) and alternate host (Corcyra cephalonica eggs)
Authors: Ali Shaukat , Peng Jing , Liang Jian-Feng , Huang Chuyang , Xie Yong-Hui , Wang Xingmin 
Published: March 2023

AbstractBackgroundThe mass production of natural predators with prolonged shelf life is a prerequisite for their field application as pest control agents. The traditional methods used for the mass production ofSerangium japonicumrely heavily on the consistent supply of natural prey. This study explains the effects ofB. tabaci(natural prey) andC. cephalonicaeggs (alternative food) on life history and transcriptome profile ofS. japanicum.MethodsThis study compares the effects ofB. tabaci(natural prey) andC. cephalonicaeggs (alternative food) on biology, reproduction, and predatory efficacy, and transcriptome profile ofS. japanicum.ResultsThis study revealed thatS. japonicumwas able to successfully complete its life cycle while feeding onB. tabaci(natural prey) andC. cephalonicaeggs (alternative food). TheC. cephalonicaeggs fedS. japonicumindividuals had longer developmental period and lower fecundity as compared to those feeding on whitefly but the survival rates (3rd instar nymphs, 4th instar nymphs and pupae) and predatory efficacy ofC. cephalonicaeggs fedS. japonicumindividuals were significantly similar to to those feeding on whitefly.Transcriptome analysis showed that when faced with dietary changes,S. japanicumcould successfully feed onC. cephalonicaeggs by regulating genes related to nutrient transport, metabolism, and detoxification. Moreover,S. japanicumdegraded excess cellular components through ribosomal autophagy and apoptosis, which provided sufficient materials and energy for survival and basic metabolism.ConclusionCorcyra cephalonicaeggs can be used as an alternate host for the predator,Serangium japonicum,as the survival rates and predatory efficacy of the predator are similar to those feeding on the natural host (B.tabaci). When faced with dietary changes,S. japanicumcould successfully feed onC. cephalonicaeggs as revealed by upregulation of genes related to nutrient transport, metabolism, and detoxification. These findings are of great significance for studying the functional evolution ofS. japonicumin response to dietary changes.