bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping Large-Scale Climate Variability to Hydrological Extremes: An Application of the Linear Inverse Model to Subseasonal Prediction
Authors: Tseng Kai-Chih , Johnson Nathaniel C. , Maloney Eric D. , Barnes Elizabeth A. , Kapnick Sarah B. 
Published: February 2021

AbstractThe excitation of the Pacific–North American (PNA) teleconnection pattern by the Madden–Julian oscillation (MJO) has been considered one of the most important predictability sources on subseasonal time scales over the extratropical Pacific and North America. However, until recently, the interactions between tropical heating and other extratropical modes and their relationships to subseasonal prediction have received comparatively little attention. In this study, a linear inverse model (LIM) is applied to examine the tropical–extratropical interactions. The LIM provides a means of calculating the response of a dynamical system to a small forcing by constructing a linear operator from the observed covariability statistics of the system. Given the linear assumptions, it is shown that the PNA is one of a few leading modes over the extratropical Pacific that can be strongly driven by tropical convection while other extratropical modes present at most a weak interaction with tropical convection. In the second part of this study, a two-step linear regression is introduced that leverages a LIM and large-scale climate variability to the prediction of hydrological extremes (e.g., atmospheric rivers) on subseasonal time scales. Consistent with the findings of the first part, most of the predictable signals on subseasonal time scales are determined by the dynamics of the MJO–PNA teleconnection while other extratropical modes are important only at the shortest forecast leads.
Climate Variability, Drought, and the Belief that High Gods Are Associated with Weather in Nonindustrial Societies
Authors: Ember Carol R. , Skoggard Ian , Felzer Benjamin , Pitek Emily , Jiang Mingkai 
Published: February 2021

AbstractAll societies have religious beliefs, but societies vary widely in the number and type of gods in which they believe as well as their ideas about what the gods do. In many societies, a god is thought to be responsible for weather events. In some of those societies, a god is thought to cause harm with weather and/or can choose to help, such as by bringing needed rain. In other societies, gods are not thought to be involved with weather. Using a worldwide, largely nonindustrial sample of 46 societies with high gods, this research explores whether certain climate patterns predict the belief that high gods are involved with weather. Our major expectation, largely supported, was that such beliefs would most likely be found in drier climates. Cold extremes and hot extremes have little or no relationship to the beliefs that gods are associated with weather. Since previous research by Skoggard et al. showed that greater resource stress predicted the association of high gods with weather, we also tested mediation path models to help us evaluate whether resource stress might be the mediator explaining the significant associations between drier climates and high god beliefs. The climate variables, particularly those pertaining to dryness, continue to have robust relationships to god beliefs when controlling on resource stress; at best, resource stress has only a partial mediating effect. We speculate that drought causes humans more anxiety than floods, which may result in the greater need to believe supernatural beings are not only responsible for weather but can help humans in times of need.
The Anti-PD-1/PD-L1 Immunotherapy for Gastric Esophageal Cancer: A Systematic Review and Meta-Analysis and Literature Review
Authors: Chen Ke , Wang Xiao , Yang Liu , Chen Zheling 
Published: February 2021

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.
Outcomes of Management of Recurrent Dupuytren Contracture: A Systematic Review and Meta-analysis
Authors: Wong Chloe R. , Huynh Minh N. Q. , Fageeh Rotana , McRae Matthew C. 
Published: February 2021

Background: With numerous treatment modalities available, it is unclear whether the treatment of recurrent Dupuytren disease is as effective as its initial treatment. We aimed to investigate the outcomes of management of recurrent Dupuytren contracture. Methods: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, MEDLINE, Embase, PubMed, CINAHL, and Cochrane Central Register of Controlled Trials were searched from their inception to April 2020. Studies of patients aged above 18 years undergoing treatment for recurrent Dupuytren contractures were included. The Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment. The study was registered with Open Science Foundation. Results: A systematic review identified 12 studies: 311 patients with 224 affected digits—index (n = 5; 2.2%), long (n = 17; 7.6%), ring (n = 57; 25.4%), small (n = 112; 50%), and unspecified (n = 33; 14.7%); of these, there were 76 metacarpophalangeal joints (MCPJ; 45.5%), 90 proximal phalangeal joints (PIPJ; 53.9%), and 1 distal interphalangeal joint (0.6%). Previous treatment included the following: percutaneous needle aponeurotomy (n = 103 of 311 patients; 33.1%), collagenase clostridium histolyticum-injection (CCH; n = 75 of 311; 24.1%), limited fasciectomy (LF) ± skin graft (n = 83 of 311; 26.7%), fasciotomy (n = 1 of 311; 0.3%), and unspecified (n = 64 of 311; 20.6%). Recurrence was treated by percutaneous needle aponeurotomy (n = 68 of 311 patients; 21.9%); CCH injection (n = 53 of 311; 17.0%); aponeurotomy or dermofasciectomy or LF (n = 176 of 311; 56.6%); ray/digit amputation (n = 8 of 311; 2.6%); and PIPJ arthrodesis (n = 6 of 293; 2.0%). Range of motion was improved by 23.31° (95% confidence interval [CI] = 13.13°-33.50°; I2 = 67%; P = .05) and 15.49° (95% CI = 2.67°-28.31°; I2 = 76%; P = .01) for MCPJ and PIPJ, respectively. Conclusions: There is low level of evidence that both surgical and nonsurgical treatments provide clinically important improvements for recurrent Dupuytren contracture.
Shoulder Pain Diagnosis, Treatment and Referral Guidelines for Primary, Community and Intermediate Care
Authors: Rees Jonathan L , Kulkarni Rohit , Rangan Amar , Jaggi Anju , Brownson Peter , Thomas Michael , Clark David , Jenkins Paul , Candal-Couto Jaime , Shahane Shantanu , Peach Christopher , Falworth Mark , Drew Stephen , Trusler Julia , Turner Phillip , Molloy Aoife 
Published: February 2021

[Formula: see text][Formula: see text] These care pathway guidelines for the shoulder have been written in collaboration with the NHS Evidence Based Interventions (EBI) programme. The EBI programme is a partnership between the Academy of Medical Royal Colleges, NHS Clinical Commissioners, the National Institute for Health and Care Excellence, as well as NHS England and Improvement
An analysis of survival in patients with castrate-resistant prostate cancer receiving enzalutamide with treatment breaks
Authors: Rowe Michael P , Walter Stuart , Hidayat Ayesha , Pollard Adam , Norris Timothy , Victor Deborah , McGrane John , Thomson Alastair 
Published: February 2021

Objective: Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned. Results: A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001). Conclusion: Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further. Level of evidence: Level 2c.
Comparison of central corneal thickness measurements with three different optical devices
Authors: Üçer Mehmet Barış , Bozkurt Erdinç 
Published: February 2021

Purpose: The purpose of this study was to compare and evaluate the agreement of central corneal thickness (CCT) values obtained with three different devices working according to optical principle in healthy eyes. Methods: 60 eyes of 60 individuals (30 men and 30 women) were enrolled in this study. CCT measurements performed with Scheimpflug–Placido topographer (Sirius), spectral-domain optical coherence tomography (RTVue) with an anterior segment module, and optical biometer (AL-Scan) were compared. Bland–Altman analysis was used to demonstrate agreement between methods. Results: The mean age was 30.07 ± 7.313 years (range, 18–47 years). The mean CCT values obtained by RTVue, Sirius, and AL-Scan were 518.25 ± 36.38 µm, 526.08 ± 36.33 µm, and 513.50 ± 39.09 µm, respectively. The mean differences in CCT were 7.83 ± 14.15 µm between Sirius and RTVue, 12.58 ± 11.87 µm between Sirius and AL-Scan, and 4.75 ± 4.50 µm between RTVue and AL-Scan. The mean CCT was statistically different among the three groups ( p < 0.05). All three modalities of CCT measurements correlated closely with each other, with Pearson’s correlation coefficients ranging from 0.924 to 0.961. The 95% limits of agreement were −19.90 to 35.56 µm between Sirius and RTVue, −10.69 to 35.85 µm between Sirius and AL-Scan, and −4.07 to 13.58 µm between RTVue and AL-Scan. Conclusion: Different results could be obtained through different noncontact devices in CCT measurements. Although the measurement values obtained by these devices show a high level of correlation, it would be a more correct approach to not use them directly interchangeably in clinical practice. Evaluation and follow-up of CCT should be performed using the same device.
The TPOCS-self-reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY): A case study of pragmatic measure development
Authors: Becker-Haimes Emily M , Klein Melanie R , McLeod Bryce D , Schoenwald Sonja K , Dorsey Shannon , Hogue Aaron , Fugo Perrin B , Phan Mary L , Hoffacker Carlin , Beidas Rinad S 
Published: February 2021

Background: Developing pragmatic assessment tools to measure clinician use of evidence-based practices is critical to advancing implementation of evidence-based practices in mental health. This case study details our community-partnered process of developing the Therapy Process Observation Coding Scale-Self-Reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY), a pragmatic, clinician-report instrument to measure cognitive behavioral therapy (CBT) delivery. Approach: We describe a five-step community-partnered development process. Initial goals were to create a self-report instrument that paralleled an existing direct observation measure of clinician delivery of CBT use to facilitate later assessment of measure performance. Cognitive interviews with community clinicians ( n = 6) and consultation with CBT experts ( n = 6) were used to enhance interpretability and usability as part of an iterative refinement process. The instrument was administered to 247 community clinicians along with an established self-reported measure of clinician delivery of CBT and other treatments to assess preliminary psychometric performance. Preliminary psychometrics were promising. Conclusion: Our community-partnered development process showed promising success and can guide future development of pragmatic implementation measures both to facilitate measurement of ongoing implementation efforts and future research aimed at building learning mental health systems. Plain language summary Developing brief, user-friendly, and accurate tools to measure how therapists deliver cognitive behavioral therapy (CBT) in routine practice is important for advancing the reach of CBT into community settings. To date, developing such “pragmatic” measures has been difficult. There is little known about how researchers can best develop these types of assessment tools so that they (1) are easy for clinicians in practice to use and (2) provide valid and useful information about implementation outcomes. As a result, there are few well-validated measures in existence that measure therapist use of CBT that are feasible for use in community practice. This paper contributes to the literature by describing our community-partnered process for developing a measure of therapist use of CBT (Therapy Process Observation Coding Scale -Self-Reported Therapist Intervention Fidelity for Youth; TPOCS-SeRTIFY). This descriptive case study outlines the community-partnered approach we took to develop this measure. This case study will contribute to future research by serving as a guide to others aiming to develop pragmatic implementation measures. In addition, the TPOCS-SeRTIFY is a pragmatic measure of clinician use of CBT that holds promise for its use by both researchers and clinicians to measure the success of CBT implementation efforts.
In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice
Authors: Li Chang , Georgakopoulou Aphrodite , Mishra Arpit , Gil Sucheol , Hawkins R. David , Yannaki Evangelia , Lieber André 
Published: February 2021

Abstract
Base editors are capable of installing precise genomic alterations without creating double-strand DNA breaks. In this study, we targeted critical motifs regulating γ-globin reactivation with base editors delivered via HDAd5/35++ vectors. Through optimized design, we successfully produced a panel of cytidine and adenine base editor (ABE) vectors targeting the erythroid BCL11A enhancer or recreating naturally occurring hereditary persistence of fetal hemoglobin (HPFH) mutations in the HBG1/2 promoter. All 5 tested vectors efficiently installed target base conversion and led to γ-globin reactivation in human erythroid progenitor cells. We observed ~23% γ-globin protein production over β-globin, when using an ABE vector (HDAd-ABE-sgHBG-2) specific to the –113A&gt;G HPFH mutation. In a β-YAC mouse model, in vivo hematopoietic progenitor/stem cell (HSPC) transduction with HDAd-ABE-sgHBG-2 followed by in vivo selection resulted in &gt;40% γ-globin+ erythrocytes in the peripheral blood. This result corresponded to 21% γ-globin production over human β-globin. The average –113A&gt;G conversion in total bone marrow cells was 20%. No alterations in hematological parameters, erythropoiesis, and bone marrow cellular composition were observed after treatment. No detectable editing was found at top-scoring, off-target genomic sites. Bone marrow lineage–negative cells from primary mice were capable of reconstituting secondary transplant-recipient mice with stable γ-globin expression. Importantly, the advantage of base editing over CRISPR/Cas9 was reflected by the markedly lower rates of intergenic HBG1/2 deletion and the absence of detectable toxicity in human CD34+ cells. Our observations suggest that HDAd-vectorized base editors represent a promising strategy for precise in vivo genome engineering for the treatment of β-hemoglobinopathies.
The NOTCH-HES-1 axis is involved in promoting Th22 cell differentiation
Authors: Zeng Chong , Shao Zhongbao , Wei Zibo , Yao Jie , Wang Weidong , Yin Liang , YangOu Huixian , Xiong Dan 
Published: February 2021

Abstract
Background
NOTCH signaling has been shown to play a role in the production of interleukin-22 (IL-22) by CD4+ T cells. Multiple T-helper (Th) cell populations secrete IL-22. Th22 (CD4+IL22+IFNγ−IL17A−) cells are a subgroup of CD4+ effector T cells that primarily generate IL-22. The regulatory mechanisms of the NOTCH signaling pathway involved in differentiation of the Th22 cell subset have not been completely elucidated. This study aimed to further explore the involvement of NOTCH signaling in Th22 differentiation.

Methods
In vitro combination of IL-6, IL-23, and tumor necrosis factor-α (TNF-α) treatment with naïve CD4+ T cells established the Th22 cell induced model. NOTCH signaling was activated by jagged-1 and inhibited by (2S)-N-[(3,5-difluorophenyl) acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester (DAPT). HES-1 siRNA and HES-1 vector were employed to knock down and induce overexpression of HES-1 to investigate the effect of NOTCH signaling on the differentiation of CD4+T cells into Th22 cells.

Results
We observed that the proportion of Th22 cells, along with Hes-1, Ahr, and Il-22 mRNA and protein expression, was increased by both jagged-1 and overexpression of HES-1. On the other hand, after the combined cytokine treatment of cells, and exposure to jagged-1 and DAPT or HES-1 siRNA, there was a decrease in the Th22 cell proportion, mRNA and protein expression of HES-1, AHR, and IL-22.

Conclusions
Our study demonstrates that HES-1 enhancement in AHR and IL-22 up-regulation of NOTCH signaling can promote the skewing of naïve CD4+T cells toward Th22 cells. Also, the results of our study show that HES-1 is a crucial factor in Th22 cell differentiation.
Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer
Authors: Li Zihaoran , Wu Xinghan , Wang Wenyu , Gai Chengcheng , Zhang Weifen , Li Wentong , Ding Dejun 
Published: February 2021

AbstractSuppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.
Automatic reconstruction of metabolic pathways from identified biosynthetic gene clusters
Authors: Sulheim Snorre , Fossheim Fredrik A. , Wentzel Alexander , Almaas Eivind 
Published: February 2021

Abstract
Background
A wide range of bioactive compounds is produced by enzymes and enzymatic complexes encoded in biosynthetic gene clusters (BGCs). These BGCs can be identified and functionally annotated based on their DNA sequence. Candidates for further research and development may be prioritized based on properties such as their functional annotation, (dis)similarity to known BGCs, and bioactivity assays. Production of the target compound in the native strain is often not achievable, rendering heterologous expression in an optimized host strain as a promising alternative. Genome-scale metabolic models are frequently used to guide strain development, but large-scale incorporation and testing of heterologous production of complex natural products in this framework is hampered by the amount of manual work required to translate annotated BGCs to metabolic pathways. To this end, we have developed a pipeline for an automated reconstruction of BGC associated metabolic pathways responsible for the synthesis of non-ribosomal peptides and polyketides, two of the dominant classes of bioactive compounds.

Results
The developed pipeline correctly predicts 72.8% of the metabolic reactions in a detailed evaluation of 8 different BGCs comprising 228 functional domains. By introducing the reconstructed pathways into a genome-scale metabolic model we demonstrate that this level of accuracy is sufficient to make reliable in silico predictions with respect to production rate and gene knockout targets. Furthermore, we apply the pipeline to a large BGC database and reconstruct 943 metabolic pathways. We identify 17 enzymatic reactions using high-throughput assessment of potential knockout targets for increasing the production of any of the associated compounds. However, the targets only provide a relative increase of up to 6% compared to wild-type production rates.

Conclusion
With this pipeline we pave the way for an extended use of genome-scale metabolic models in strain design of heterologous expression hosts. In this context, we identified generic knockout targets for the increased production of heterologous compounds. However, as the predicted increase is minor for any of the single-reaction knockout targets, these results indicate that more sophisticated strain-engineering strategies are necessary for the development of efficient BGC expression hosts.