bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review evaluating the efficacy of the cerebroplacental ratio (CPR) in saving babies lives
Authors: Elmes Catherine , Phillips Rita 
Published: October 2021

Introduction The aim of this systematic review is to critically assess the efficacy of the cerebroplacental ratio performed in the third trimester at predicting adverse perinatal outcomes and reducing stillbirth rates. Method The literature search was performed using CINAHL, EMBASE, EMCARE, MEDLINE and PubMed including systematic reviews, retrospective and prospective studies from inception until July 2020 utilising the PRISMA checklist and flowchart. Data displaying sensitivities, specificity and odds ratios (OR) to include 95% confidence interval (CI) were extracted and synthesised. Findings Initially, 1226 studies were identified, and nine studies met the inclusion criteria. Sample sizes ranged from 491 to 9772 pregnancies. The cerebroplacental ratio had the strongest diagnostic accuracy of all of the independent variables for detecting fetal demise (mean sensitivity and specificity; 79% and 78%). The cerebroplacental ratio, however, did not perform as favourably at predicting operative delivery (mean sensitivity and specificity; 59% and 82%) or anticipating admission to the neonatal intensive care unit (mean sensitivity and specificity; 55% and 74%). Discussion The results from this study showed that the cerebroplacental ratio within third trimester pregnancies has been proven to have moderate to high diagnostic value when detecting adverse perinatal outcomes, in particular fetal demise. Conclusion Cerebroplacental ratio has the potential as a diagnostic tool to reduce adverse perinatal outcomes, in particular fetal demise and help reduce stillbirth rates. The main study limitation involved heterogeneity within the included studies, in particular with a regard to blinding.
Efficacy and Safety of Subcutaneous Immunotherapy for Local Allergic Rhinitis: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhu Wanting , Gao Pei , Zhang Qidi , Chen Jianjun 
Published: October 2021

Background Subcutaneous immunotherapy (SCIT) has been used for treating local allergic rhinitis (LAR) patients. However, the clinical efficacy and safety were still questioned. Objective This study was designed to estimate the efficacy and safety of SCIT for treating LAR patients through meta-analysis. Methods We systemically searched MEDLINE, Cochrane Library, and Embase publications. Randomized, double-blind, clinical trials for the efficacy and safety of Allergen Immunotherapy (AIT) for LAR were included. A meta-analysis of 4 clinical endpoints (combined symptom and medication scores [CSMS], symptom scores [SS], medication scores [MS] and rhinoconjunctivitis quality of life questionnaire [RQLQ]) and adverse events (AEs)) was performed after bias and heterogeneity assessments. The immunologic response results were summarized. Results Four RCTs with 134 patients were included. Four studies for analyzing primary outcomes (CSMS, SS, MS) and AEs, three for RQLQ results. The results indicated an important significant difference between SCIT and placebo groups, list as follows: CSMS (SMD = −2.42, 95% CI: −3.60 to −1.25, P < .0001), SS (SMD = −2.08, 95% CI −3.68 to −0.48, P = .01), MS (SMD = −1.43, 95% CI: −2.65 to −0.21, P = 0.02), RQLQ (SMD = −0.70, 95% CI −1.29 to −0.12, P = .02), Local AEs (RR = 4.13, 95% CI 1.08 to 15.77, P = .04). For immunologic response, significantly increased serum sIgG4 levels and improvements of allergen tolerance was observed after SCIT. Conclusions Our meta-analysis suggests that SCIT has a significant effect on improving symptoms and reducing medicine consumption for LAR patients. Larger and multicenter clinical trials are needed to clarify the safety and long-term efficacy.
Tyrosine phosphatases regulate resistance to ALK inhibitors in ALK+ anaplastic large cell lymphoma
Authors: Karaca Atabay Elif , Mecca Carmen , Wang Qi , Ambrogio Chiara , Mota Ines , Prokoph Nina , Mura Giulia , Martinengo Cinzia , Patrucco Enrico , Leonardi Giulia , Hossa Jessica , Pich Achille , Mologni Luca , Gambacorti-Passerini Carlo , Brugières Laurence , Geoerger Birgit , Turner Suzanne D. , Voena Claudia , Cheong Taek-Chin , Chiarle Roberto 
Published: October 2021

Abstract
Anaplastic large cell lymphomas (ALCLs) frequently carry oncogenic fusions involving the anaplastic lymphoma kinase (ALK) gene. Targeting ALK using tyrosine kinase inhibitors (TKIs) is a therapeutic option in cases relapsed after chemotherapy, but TKI resistance may develop. By applying genomic loss-of-function screens, we identified PTPN1 and PTPN2 phosphatases as consistent top hits driving resistance to ALK TKIs in ALK+ ALCL. Loss of either PTPN1 or PTPN2 induced resistance to ALK TKIs in vitro and in vivo. Mechanistically, we demonstrated that PTPN1 and PTPN2 are phosphatases that bind to and regulate ALK phosphorylation and activity. In turn, oncogenic ALK and STAT3 repress PTPN1 transcription. We found that PTPN1 is also a phosphatase for SHP2, a key mediator of oncogenic ALK signaling. Downstream signaling analysis showed that deletion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK, and JAK/STAT pathways. RNA sequencing of patient samples that developed resistance to ALK TKIs showed downregulation of PTPN1 and PTPN2 associated with upregulation of SHP2 expression. Combination of crizotinib with a SHP2 inhibitor synergistically inhibited the growth of wild-type or PTPN1/PTPN2 knock-out ALCL, where it reverted TKI resistance. Thus, we identified PTPN1 and PTPN2 as ALK phosphatases that control sensitivity to ALK TKIs in ALCL and demonstrated that a combined blockade of SHP2 potentiates the efficacy of ALK inhibition in TKI-sensitive and -resistant ALK+ ALCL.
Evaluation of vecabrutinib as a model for noncovalent BTK/ITK inhibition for treatment of chronic lymphocytic leukemia
Authors: Jebaraj Billy Michael Chelliah , Müller Annika , Dheenadayalan Rashmi Priyadharshini , Endres Sascha , Roessner Philipp M. , Seyfried Felix , Walliser Claudia , Wist Martin , Qi Jialei , Tausch Eugen , Mertens Daniel , Fox Judith A. , Debatin Klaus-Michael , Meyer Lüder Hinrich , Taverna Pietro , Seiffert Martina , Gierschik Peter , Stilgenbauer Stephan 
Published: October 2021

AbstractCovalent Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib, have proven to be highly beneficial in the treatment of chronic lymphocytic leukemia (CLL). Interestingly, the off-target inhibition of IL-2-inducible T-cell kinase (ITK) by ibrutinib may also play a role in modulating the tumor microenvironment, potentially enhancing the treatment benefit. However, resistance to covalently binding BTK inhibitors can develop as the result of a mutation in cysteine 481 of BTK (C481S), which prevents irreversible binding of the drugs. In the present study we performed preclinical characterization of vecabrutinib, a next-generation noncovalent BTK inhibitor that has ITK-inhibitory properties similar to those of ibrutinib. Unlike ibrutinib and other covalent BTK inhibitors, vecabrutinib showed retention of the inhibitory effect on C481S BTK mutants in vitro, similar to that of wild-type BTK. In the murine Eμ-TCL1 adoptive transfer model, vecabrutinib reduced tumor burden and significantly improved survival. Vecabrutinib treatment led to a decrease in CD8+ effector and memory T-cell populations, whereas the naive populations were increased. Of importance, vecabrutinib treatment significantly reduced the frequency of regulatory CD4+ T cells in vivo. Unlike ibrutinib, vecabrutinib treatment showed minimal adverse impact on the activation and proliferation of isolated T cells. Lastly, combination treatment with vecabrutinib and venetoclax augmented treatment efficacy, significantly improved survival, and led to favorable reprogramming of the microenvironment in the murine Eμ-TCL1 model. Thus, noncovalent BTK/ITK inhibitors, such as vecabrutinib, may be efficacious in C481S BTK mutant CLL while preserving the T-cell immunomodulatory function of ibrutinib.
All-trans retinoic acid plus low-dose rituximab vs low-dose rituximab in corticosteroid-resistant or relapsed ITP
Authors: Wu Ye-Jun , Liu Hui , Zeng Qiao-Zhu , Liu Yi , Wang Jing-Wen , Wang Wen-Sheng , Jia-Feng  , Zhou He-Bing , Huang Qiu-Sha , He Yun , Fu Hai-Xia , Zhu Xiao-Lu , Jiang Qian , Jiang Hao , Chang Ying-Jun , Xu Lan-Ping , Huang Xiao-Jun , Zhang Xiao-Hui 
Published: October 2021

Abstract
The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count &gt;30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.
Fast activation maximization for molecular sequence design
Authors: Linder Johannes , Seelig Georg 
Published: October 2021

Abstract
Background
Optimization of DNA and protein sequences based on Machine Learning models is becoming a powerful tool for molecular design. Activation maximization offers a simple design strategy for differentiable models: one-hot coded sequences are first approximated by a continuous representation, which is then iteratively optimized with respect to the predictor oracle by gradient ascent. While elegant, the current version of the method suffers from vanishing gradients and may cause predictor pathologies leading to poor convergence.

Results
Here, we introduce Fast SeqProp, an improved activation maximization method that combines straight-through approximation with normalization across the parameters of the input sequence distribution. Fast SeqProp overcomes bottlenecks in earlier methods arising from input parameters becoming skewed during optimization. Compared to prior methods, Fast SeqProp results in up to 100-fold faster convergence while also finding improved fitness optima for many applications. We demonstrate Fast SeqProp’s capabilities by designing DNA and protein sequences for six deep learning predictors, including a protein structure predictor.

Conclusions
Fast SeqProp offers a reliable and efficient method for general-purpose sequence optimization through a differentiable fitness predictor. As demonstrated on a variety of deep learning models, the method is widely applicable, and can incorporate various regularization techniques to maintain confidence in the sequence designs. As a design tool, Fast SeqProp may aid in the development of novel molecules, drug therapies and vaccines.
Predictive scoring systems for in-hospital mortality due to acutely decompensated liver cirrhosis in Indonesia
Authors: Nababan Saut Horas H. , Mansjoer Arif , Fauzi Achmad , Gani Rino A. 
Published: October 2021

Abstract
Background
Acutely decompensated liver cirrhosis is associated with high medical costs and negatively affects productivity and quality of life. Data on factors associated with in-hospital mortality due to acutely decompensated liver cirrhosis in Indonesia are scarce. This study aims to identify predictors of in-hospital mortality and develop predictive scoring systems for clinical application in acutely decompensated liver cirrhosis patients.

Methods
This was a retrospective cohort study using a hospital database of acutely decompensated liver cirrhosis data at Cipto Mangunkusumo National General Hospital, Jakarta (2016–2019). Bivariate and multivariate logistic regression analyses were performed to identify the predictors of in-hospital mortality. Two scoring systems were developed based on the identified predictors.

Results
A total of 241 patients were analysed; patients were predominantly male (74.3%), had hepatitis B (38.6%), and had Child–Pugh class B or C cirrhosis (40% and 38%, respectively). Gastrointestinal bleeding was observed in 171 patients (70.9%), and 29 patients (12.03%) died during hospitalization. The independent predictors of in-hospital mortality were age (adjusted OR: 1.09 [1.03–1.14]; p = 0.001), bacterial infection (adjusted OR: 6.25 [2.31–16.92]; p < 0.001), total bilirubin level (adjusted OR: 3.01 [1.85–4.89]; p < 0.001) and creatinine level (adjusted OR: 2.70 [1.20–6.05]; p = 0.016). The logistic and additive scoring systems, which were developed based on the identified predictors, had AUROC values of 0.899 and 0.868, respectively.

Conclusion
The in-hospital mortality rate of acutely decompensated liver cirrhosis in Indonesia is high. We have developed two predictive scoring systems for in-hospital mortality in acutely decompensated liver cirrhosis patients.
Do older people with cardiovascular-metabolic multimorbidity prefer to sign contracts for family doctor services? Evidence from a cross-sectional study in rural Shandong, China
Authors: Yang Shijun , Li Jie , Fu Peipei , Chen Yan , Wang Yi , Zhao Dan , Li Zhixian , Li Wenjuan , Li Jie , Yan Chen , Gui Zhen , Zhou Chengchao 
Published: October 2021

Abstract
Background
Family doctor policy is an important part of deepening healthcare reform in China. The study aimed to explore the association between cardiovascular-metabolic multimorbidity and the status of signing a contract for family doctor services among the older people in rural Shandong, China.

Methods
A cross-sectional study was conducted in 3 cities of Shandong province, China. A total of 1395 rural residents over 60 years of age were included in this study using a multistage stratified random sampling method. Covariates included demographic and socioeconomic characteristics, health-related characteristics, health service utilization, and awareness of family doctor contract services. The univariate and multivariate regression logistic analysis was used to analyze the data.

Results
There were 28.2% of the rural older people contracted for the family doctor contract services. The contract rate of seniors with cardiovascular-metabolic multimorbidity was statistically higher than those without cardiovascular-metabolic multimorbidity (OR = 1.67, 95%CI, 1.21-2.32) after controlling for confounding factors. In addition, occupation, physical activities, self-rated health status, distance from the village clinic, the awareness of family doctor contract services were found to be associated with the signing behavior among the rural older adults.

Conclusion
This study demonstrated that the rural older people with cardiovascular-metabolic multimorbidity had a higher family doctor contract rate than those without cardiovascular-metabolic multimorbidity, and there was a gap between the current signing rate and the policy goal. To increase the rate of signing for family doctor contract services, the government should take joint efforts to expand the publicity and coverage, and give priority to meeting the healthcare demands of rural older adults with cardiovascular-metabolic multimorbidity.
The COVID-19 pandemic as experienced by the spouses of home-dwelling people with dementia – a qualitative study
Authors: Rokstad Anne Marie Mork , Røsvik Janne , Fossberg Marit , Eriksen Siren 
Published: October 2021

Abstract
Background
Worldwide, restrictive measures have been taken to manage the spread of the COVID-19 pandemic. Social distancing and self-isolation have considerably affected the lives of people with dementia and their informal caregivers. The purpose of the study was to explore the consequences of the COVID-19 pandemic as experienced by the spouses of home-dwelling people with dementia in Norway.

Methods
The study had a qualitative descriptive design using individual telephone interviews for data collection. A total sample of 17 spouses of people with dementia were included, 14 women and three men ages 52 to 82 years. A qualitative content analysis following six steps inspired by Graneheim and Lundman was used to identify the categories presented.

Results
The participants emphasized four main perspectives: 1) Radical changes in available services, 2) Restrictions changed everyday life, 3) Impacts on health and well-being, and 4) Actions that made life easier. The participants also described how positive activities and easily accessible services helped them in this situation.

Conclusions
The governmental restrictions of the COVID-19 pandemic resulted in radical changes in available services with severe consequences for the lives and well-being of home-dwelling people with dementia and their spouses. Examples of coping strategies and possible psychosocial interventions compatible with virus precautions were identified. The potential of such interventions should be further explored to meet the needs of vulnerable groups in situations like a pandemic.
Disparity of perception of quality of life between head and neck cancer patients and caregivers
Authors: Kassir Zachary M. , Li Jinhong , Harrison Christine , Johnson Jonas T. , Nilsen Marci L. 
Published: October 2021

Abstract
Background
Caregivers are invaluable sources of support for individuals recovering from head and neck cancer (HNC). Accordingly, minimizing caregiver distress is essential to promote the well-being of both caregivers and their patients. This study assessed if psychosocial distress (i.e., anxiety and depression) among HNC caregivers is associated with a difference in how caregivers and their patients perceive patients’ quality of life (QOL) after treatment completion.

Methods
Caregivers’ and patients’ perceptions of patient QOL were assessed using the University of Washington QOL Questionaire (UWQOL), a validated HNC-specific health-related QOL questionnaire. The survey is interpreted in terms of its two composite scores: a physical QOL score and a social-emotional QOL score with higher scores indicating better QOL. Caregiver anxiety was assessed using the Generalized Anxiety Questionaire-7 (GAD-7) and caregiver depression was assessed using the Patient Health Questionaire 8 (PHQ-8). Patients completed the UWQOL as part of clinic intake while caregivers were asked to complete the UWQOL for their patients in addition to the PHQ-8 and GAD-7 in private. Linear regression was used to analyze the association between differences in caregivers’ and patients’ QOL scores (both social-emotional and physical QOL subscale scores) and GAD-7 and PHQ-8 scores.

Results
Of 47 caregivers recruited, 42.6% (n = 20) viewed patients’ social-emotional QOL more negatively than patients themselves, while 31.9% viewed patients’ physical QOL more negatively. After controlling for covariates, differences in perception of social-emotional QOL (p = .01) and differences in perception of physical QOL (p = .007) were significantly associated with caregiver depression, but not anxiety. Caregivers who disagreed with patients regarding patients’ social-emotional QOL scored 6.80 points higher on the PHQ8 than agreeing caregivers. Caregivers who disagreed regarding patients’ physical QOL scored 6.09 points higher.

Conclusion
Caregivers commonly view patients’ QOL more negatively than patients themselves. These caregivers tend to have greater psychosocial distress than caregivers who agree with their patients. Interventions designed to identify and aid at-risk caregivers are critically needed. We propose screening for differences in perception of patient QOL as a way of identifying distressed caregivers as well as provider-facilitated communication between patients and caregivers as possible interventions that should be examined in future research.
Artificial neural network application for identifying risk of depression in high school students: a cross-sectional study
Authors: Zhao Fang-Fang 
Published: October 2021

AbstractBackgroundIdentifying important factors contributing to depression is necessary for interrupting risk pathways to minimize adolescent depression. The study aimed to assess the prevalence of depression in high school students and develop a model for identifying risk of depression among adolescents.MethodsCross-sectional study was conducted. A total of 1190 adolescents from two high schools in eastern China participated in the study. Artificial neurol network (ANN) was used to establish the identification model.ResultsThe prevalence of depression was 29.9% among the students. The model showed the top five protective and risk factors including perceived stress, life events, optimism, self-compassion and resilience. ANN model accuracy was 81.06%, with sensitivity 65.3%, specificity 88.4%, and area under the receiver operating characteristic (ROC) curves 0.846 in testing dataset.ConclusionThe ANN showed the good performance in identifying risk of depression. Promoting the protective factors and reducing the level of risk factors facilitate preventing and relieving depression.
Effect of single-incision laparoscopic distal gastrectomy guided by ERAS and the influence on immune function
Authors: Zhou Junfeng , Lin Sheng , Sun Sida , Zheng Chengying , Wang Jiaxing , He Qingliang 
Published: October 2021

Abstract
Background
To evaluate the immune function of gastric cancer patients after single-incision laparoscopic distal gastrectomy (SIDG) or multiport laparoscopic distal gastrectomy (MLDG) guided by enhanced recovery after surgery (ERAS).

Methods
A retrospective cohort study was performed on 120 patients who underwent laparoscopic distal gastrectomy for gastric cancer. The patients were divided into two groups according to operation method: group A (MLDG) and group B (SIDG), both guided by ERAS concept. The indicators reflecting immune function and inflammation, such as CD3+, CD4+, CD8+ and NK cell count, CD4+/CD8+ cell ratios, IgA, IgM and IgG levels, C-reactive protein (CRP), total lymphocyte count (TLC) and neutrophil-to-lymphocyte ratio (NLR) were tested 3 days and 7 days after surgery.

Results
The skin incision length of patients in group B was significantly shorter than that in group A, but the operation time was significantly longer in group B than that in group A (P < 0.05). There were no significant differences in preoperative CD3+, CD4+, CD8+, natural killer (NK) cells, CD4+/CD8+, IgA, IgM and IgG levels between two groups (P < 0.05). Three days after surgery, the immune function indices were decreased in both groups, but with no significant difference between two groups (P > 0.05). On the 7th day after surgery, the immune indexes of both groups recovered somewhat, approaching the preoperative level (P > 0.05). Inflammation indexes increased 3 days after surgery and decreased 7 days after surgery in both groups, among them the CRP level in group A was higher than that in group B (P < 0.05). The 3-year survival rate were 96.7% in group A and 91.7% in group B, respectively, with no statistically significant difference.

Conclusion
Compared with MLDG guided by ERAS, SIDG under the guidance of the ERAS concept has better cosmetic effect and similar effect on immune function of gastric cancer patients.