bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiyear La Niña Events and Multiseason Drought in the Horn of Africa
Authors: Anderson Weston , Cook Benjamin I. , Slinski Kim , Schwarzwald Kevin , McNally Amy , Funk Chris 
Published: October 2022

Abstract
One of the primary sources of predictability for seasonal hydroclimate forecasts are sea surface temperatures (SSTs) in the tropical Pacific, including El Niño–Southern Oscillation. Multiyear La Niña events in particular may be both predictable at long lead times and favor drought in the bimodal rainfall regions of East Africa. However, SST patterns in the tropical Pacific and adjacent ocean basins often differ substantially between first- and second-year La Niñas, which can change how these events affect regional climate. Here, we demonstrate that multiyear La Niña events favor drought in the Horn of Africa in three consecutive seasons [October–December (OND), March–May (MAM), OND]. But they do not tend to increase the probability of a fourth season of drought owing to the sea surface temperatures and associated atmospheric teleconnections in the MAM long rains season following second-year La Niña events. First-year La Niñas tend to have both greater subsidence over the Horn of Africa, associated with warmer waters in the west Pacific that enhance the Walker circulation, and greater cross-continental moisture transport, associated with a warm tropical Atlantic, as compared to second-year La Niñas. Both the increased subsidence and enhanced cross-continental moisture transport favors drought in the Horn of Africa. Our results provide a physical understanding of the sources and limitations of predictability for using multiyear La Niña forecasts to predict drought in the Horn of Africa.
25-year Follow-up of Primary Tibial Periosteal Graft for Hard Palate Repair in Cleft Lip and Palate: Outcomes, Concerns and Controversies
Authors: Rizzo Maria Ida , Cajozzo Marta , Bucci Daria , Pistoia Angelica , Palmieri Annapina , Rajabtork Zadeh Oriana , Palmieri Giancarlo , Spuntarelli Giorgio , Zama Mario 
Published: October 2022

Objective This study evaluates long-term outcomes in adults with Unilateral and Bilateral Cleft Lip and Palate (UCLP/BCLP) treated during the period 1992 to 1995 with tibial periosteal graft in primary repair. Design Retrospective study. Setting Department of Plastic and Maxillofacial Surgery, Children's Hospital Bambino Gesù (Italy). Patients The study included 52 patients with non-syndromic BCLP/UCLP who met the inclusion criteria. Interventions All patients underwent a standardized surgical protocol using a tibial periosteal graft as primary repair of the hard palate. Main Outcome Measure(s) Long-term outcomes on maxillary growth, residual oronasal fistula, and leg length discrepancy. Results About <2% of patients showed oral–nasal communication. Mean value of maxillary depth was 86° ± 4.5°. The lower value for maxillary retrusion was 76.8° in relation to the Frankfurt plane. At the x-ray control, 12.2% of patients showed leg discrepancy with a difference of always <2 cm. Conclusions The rate of maxillary retrusion obtained was the same if compared to other techniques. Tibial periosteal graft reduces the risk of fistula and the need for reintervention after secondary bone graft. The study did not observe negative impacts on leg growth after 25 years.
Data-driven scalable pipeline using national agent-based models for real-time pandemic response and decision support
Authors: Bhattacharya Parantapa , Chen Jiangzhuo , Hoops Stefan , Machi Dustin , Lewis Bryan , Venkatramanan Srinivasan , Wilson Mandy L. , Klahn Brian , Adiga Aniruddha , Hurt Benjamin , Outten Joseph , Adiga Abhijin , Warren Andrew , Baek Young Yun , Porebski Przemyslaw , Marathe Achla , Xie Dawen , Swarup Samarth , Vullikanti Anil , Mortveit Henning , Eubank Stephen , Barrett Christopher L. , Marathe Madhav 
Published: October 2022

This paper describes an integrated, data-driven operational pipeline based on national agent-based models to support federal and state-level pandemic planning and response. The pipeline consists of ( i) an automatic semantic-aware scheduling method that coordinates jobs across two separate high performance computing systems; ( ii) a data pipeline to collect, integrate and organize national and county-level disaggregated data for initialization and post-simulation analysis; ( iii) a digital twin of national social contact networks made up of 288 Million individuals and 12.6 Billion time-varying interactions covering the US states and DC; ( iv) an extension of a parallel agent-based simulation model to study epidemic dynamics and associated interventions. This pipeline can run 400 replicates of national runs in less than 33 h, and reduces the need for human intervention, resulting in faster turnaround times and higher reliability and accuracy of the results. Scientifically, the work has led to significant advances in real-time epidemic sciences.
Characteristics of the raw materials of glazed tile bodies in the southern area of the Bao'ensi site, Nanjing, China
Authors: Zhao Weijuan , Zhao Dan , Wu Bo , Li Bo , Zhou Baohua , Cui Jianfeng , Chen Qinlong 
Published: October 2022

AbstractThe Nanjing Bao'ensi site is the largest and highest-ranking royal temple from the Ming Dynasty, and it is famous for its full-body glass pagoda. In this study, the glazed tiles excavated from the southern area of the Bao'ensi site were selected and analysed using X-ray diffraction, thermal dilation and energy-dispersive X-ray fluorescence to determine their phase composition, firing temperature and chemical composition. The glazed tile bodies of the Bao'ensi site consist mainly of quartz and mullite, although some samples contain trace amounts of other minerals. All of the body samples were fired to the same temperature range (i.e. 1000–1100°C). The firing temperature combined with the phase composition indicate that the raw materials and firing process of the glazed tile body samples have similarities, but there are certain differences. The source of the raw materials for a portion of the glazed tile bodies is Dangtu, Anhui, whilst the source of the raw materials for the remaining materials remains to be discovered.
Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial
Authors: Daver Naval G. , Dail Monique , Garcia Jacqueline S. , Jonas Brian A. , Yee Karen W. L. , Kelly Kevin R. , Vey Norbert , Assouline Sarit , Roboz Gail J. , Paolini Stefania , Pollyea Daniel A. , Tafuri Agostino , Brandwein Joseph M. , Pigneux Arnaud , Powell Bayard L. , Fenaux Pierre , Olin Rebecca L. , Visani Giuseppe , Martinelli Giovanni , Onishi Maika , Wang Jue , Huang Weize , Green Cherie , Ott Marion G. , Hong Wan-Jen , Konopleva Marina Y. , Andreeff Michael 
Published: October 2022

Abstract
This phase 1b trial (NCT02670044) evaluated venetoclax-idasanutlin in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) ineligible for cytotoxic chemotherapy. Two-dimensional dose escalation (DE, n = 50) was performed for venetoclax daily with idasanutlin on days 1 to 5 in 28-day cycles, followed by dosing schedule optimization (n = 6) to evaluate reduced venetoclax schedules (21-/14-day dosing). Common adverse events (occurring in ≥40% of patients) included diarrhea (87.3% of patients), nausea (74.5%), vomiting (52.7%), hypokalemia (50.9%), and febrile neutropenia (45.5%). During DE, across all doses, composite complete remission (CRc; CR + CR with incomplete blood count recovery + CR with incomplete platelet count recovery) rate was 26.0% and morphologic leukemia-free state (MLFS) rate was 12%. For anticipated recommended phase 2 doses (venetoclax 600 mg + idasanutlin 150 mg; venetoclax 600 mg + idasanutlin 200 mg), the combined CRc rate was 34.3% and the MLFS rate was 14.3%. Pretreatment IDH1/2 and RUNX1 mutations were associated with higher CRc rates (50.0% and 45.0%, respectively). CRc rate in patients with TP53 mutations was 20.0%, with responses noted among those with co-occurring IDH and RUNX1 mutations. In 12 out of 36 evaluable patients, 25 emergent TP53 mutations were observed; 22 were present at baseline with low TP53 variant allele frequency (median 0.0095% [range, 0.0006-0.4]). Venetoclax-idasanutlin showed manageable safety and encouraging efficacy in unfit patients with R/R AML. IDH1/2 and RUNX1 mutations were associated with venetoclax-idasanutlin sensitivity, even in some patients with co-occurring TP53 mutations; most emergent TP53 clones were preexisting. Our findings will aid ongoing/future trials of BCL-2/MDM2 inhibitor combinations. This trial was registered at www.clinicaltrials.gov as #NCT02670044.
A novel pH- and glutathione-responsive drug delivery system based on in situ growth of MOF199 on mesoporous organic silica nanoparticles targeting the hepatocellular carcinoma niche
Authors: Ling Jiaji , Jiang Yongmei , Yan Shaoying , Dang Hao , Yue Huan , Liu Kanglin , Kuang Linghan , Liu Xingxin , Tang Hua 
Published: October 2022

Abstract
Background
For people with advanced hepatocellular carcinoma (HCC), systemic chemotherapy remains the only choice of palliative treatment. However, chemotherapy efficacy is not effective due to its short blood circulation times, nonspecific cell and tissue biodistribution, and rapid metabolism or excretion from the body. Therefore, a targeted nanomedicine delivery system is urgently needed.

Methods
In order to improve the treatment efficiency of HCC, based on in situ growth of a copper metal organic framework on mesoporous organic silica nanoparticles, dual pH- and glutathione (GSH)-responsive multifunctional nanocomposites were synthesized as nanocarriers for enhanced HCC therapy. In this research, cellular uptake studies were performed using CLSM and Bio-TEM observations. Flow cytometry, AO-EB fluorescent staining, EdU test and Western blot were utilized to explore the apoptosis and proliferation process. In vivo imaging was employed to research the distribution of the nanocomposites in HCC tumor-bearing nude mice and the xenograft model of HCC tumor-bearing nude mice was applied to investigate the anti-tumor effects of drug-loaded nanocomposites in vivo.

Results
This newly constructed degradable nanocomposite DOX/SOR@SP94 and mPEG-anchored MONs@MOF199 (D/S@SPMM) has the benefits of controllable pore size, high encapsulation efficiency, and precise targeting. According to the results of in vivo imaging and anti-tumor studies, as well as pharmacokinetic research, D/S@SPMM possessed precise HCC tumor targeting and long-lasting accumulation properties at the tumor region. Compared with traditional chemotherapy and non-targeted drug delivery systems, anti-tumor efficiency was increased by approximately 10- and 5-fold, respectively. The nanocomposites exhibited excellent anti-tumor properties without inducing observable systemic toxicity, owing to efficient DOX and SOR loading and release as well as the HCC specific targeting peptide SP94.

Conclusions
The in vitro and in vivo anti-tumor results indicated that these nanocomposites could be an efficient nanomedicine for targeting HCC therapy.
Low-dose interleukin-2 can improve salivary secretion but not lymphocyte infiltration of salivary glands in a murine model of Sjögren’s syndrome
Authors: Wen Junsong , Zhu Fenglin , Yu Xi , Xie Hualing , Li Chengyin 
Published: October 2022

AbstractIntroduction/aimEffects of low-dose interleukin-2 (IL-2) on the exocrine glandular glands of Sjögren’s syndrome are unknown. The aim of this study was to investigate the effects of low-dose IL-2 on salivary gland structure and function in a murine model of Sjögren’s syndrome.Materials and methodsNon-obese diabetic/Ltj (NOD) mice were used as the animal model of Sjögren’s syndrome, and low-dose IL-2 or phosphate buffered saline was administered subcutaneously from 5 weeks of age, while ICR mice were used as controls. Some mice were sacrificed at 9 weeks of age, while the other mice that continued to receive treatment were sacrificed at 23 weeks. We determined the salivary flow rate of mice every 3 weeks during the intervention. After the mice were sacrificed, one submandibular gland was removed for pathological evaluation, while the other submandibular gland was used to measure the levels of 25 cytokines by Luminex technology. Cervical lymph nodes and spleens were examined by flow cytometry for the proportions of CD8+T cells and Treg cells.ResultsThe results showed that the salivary flow rate of NOD mice was slower than that of control-group mice, and there were more pathological changes in the submandibular gland. The levels of many cytokines in the submandibular gland were elevated. The proportion of CD8+T cells in the cervical lymph nodes and spleens was increased; however, the proportion of Treg cells was decreased. After treatment with IL-2, the exocrine function of the salivary glands of mice was improved. IL-2 also promoted the proliferation of Treg cells in the cervical lymph nodes and spleens, but it did not alter the extent of lymphocyte infiltration in the submandibular gland. The levels of cytokines in the submandibular glands, as well as the proportion of CD8+T cells in the cervical lymph nodes and spleens, were unchanged significantly after IL-2 treatment.ConclusionOur results demonstrate that treatment with low-dose IL-2 improves the secretory function of the exocrine glands of mice with Sjögren’s syndrome, but it does not reverse the structural damage of the exocrine glands.
Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes: an overview of systematic reviews
Authors: Crawford Fay , Nicolson Donald J. , Amanna Aparna E. , Smith Marie 
Published: October 2022

Abstract
Background
Reliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)].

Methods
Medline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews.

Findings
The overview identified 30 systematic reviews of patient education, footwear and off-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap.

Interpretation
The majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.
Unmet needs about iron deficiency in peritoneal dialysis: a Delphi consensus panel
Authors: Mazzaferro Sandro , D’Alonzo Silvia , Morosetti Massimo 
Published: October 2022

AbstractBackgroundAnaemia and iron deficiency (ID) are common in chronic kidney disease (CKD) patients and related to outcomes. There is growing interest about the role of iron supplementation in CKD, particularly ferric carboxymaltose (FCM), also in relation to the use of erythropoiesis stimulating agents (ESAs). Despite a greater knowledge on ID management in patients receiving haemodialysis, a paucity of data exists about peritoneal dialysis (PD). Furthermore, the aim of this paper is to provide the results of a nationwide Italian survey about ID in PD using the Delphi method.MethodsA list of 16 statements (48 items) was developed about four main topics: (1) approach to iron therapy in PD; (2) management experience about iron therapy in PD; (3) ESA and iron in PD; (4) pharmacoeconomic impact. Using the Delphi methodology, the survey was distributed online to 36 Italian nephrologists with expertise in PD, who rated their level of agreement with each item on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement.ResultsTwenty-five experts (70%) answered the survey. 35 items (73%) achieved a consensus (8 negative and 27 positive). In particular, the diagnosis of ID is widely known, but some doubts exist about how frequently test it. The use of I.V. iron seems to be routinary and can save money reducing the administration of ESAs. However, internal protocols are welcome.ConclusionsExpert PD nephrologists know well the problem of ID and feel the necessity of shared protocols to optimize the iron therapy and consequently the use of ESAs.
Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer
Authors: Zhang He-Yang , Xie Hai-Lun , Ruan Guo-Tian , Zhang Qi , Ge Yi-Zhong , Liu Xiao-Yue , Tang Meng , Song Meng-Meng , Lin Shi-Qi , Yang Ming , Zhang Xiao-Wei , Xu Hong-Xia , Song Chun-Hua , Shi Han-Ping 
Published: October 2022

Abstract
Background
Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer.

Methods
This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan–Meier and Cox proportional hazards regression models were used to analyze long-term survival.

Results
A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose–response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan–Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time.

Conclusion
The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.
Overwork among resident physicians: national questionnaire survey results
Authors: Ishikawa Masatoshi 
Published: October 2022

Abstract
Background
Residents experience the longest working hours among physicians. Thus, it would be beneficial to perform a nationwide survey in Japan on residents’ long work hours and the background factors promoting upper limits on working hours of Japanese residents. The aim of this study was to study or assess the state of physicians’ excessive work hours and its background factors using a questionnaire survey.

Methods
The survey was sent to 924 hospitals. The physicians’ general attributes, work hours and conditions, and employers’ foundational entities were explored. Multiple logistic regression analysis was performed to elucidate the background factors for long work hours.

Results
Of the 4306 resident physicians who responded, 67% had ≥ 60 in-hospital hours/week and 27% had ≥ 80 h/week; 51% were on-call ≥ four times/month. Many of them hoped for increased remuneration. Additionally, female (reference: male, OR: 0.65, 95% CI: 0.55–0.76), 35–40 years old (reference: 25–30 years old, OR: 1.83, 95% CI: 1.32–2.54), childlessness (reference: child, OR: 1.41, 95% CI: 1.12–1.75), surgical specialization (reference: internal medicine, OR: 2.51, 95% CI: 1.96–3.23), neurosurgical specialization (reference: internal medicine, OR: 4.38, 95% CI: 2.92–6.59) and hospitals with 200–400 physicians (reference: <100 physicians, OR: 1.82, 95% CI: 1.12–2.96) exhibited significant correlations with ≥ 80 in-hospital hours/week.

Conclusion
Understanding the factors that increase the likelihood of residents working very long hours could aid in making targeted changes to address the specific concerns. Moreover, reducing working hours to a reasonable limit can improve resident physicians’ health and the quality of care they provide in their community.
Federated learning algorithms for generalized mixed-effects model (GLMM) on horizontally partitioned data from distributed sources
Authors: Li Wentao , Tong Jiayi , Anjum Md. Monowar , Mohammed Noman , Chen Yong , Jiang Xiaoqian 
Published: October 2022

Abstract
Objectives
This paper developed federated solutions based on two approximation algorithms to achieve federated generalized linear mixed effect models (GLMM). The paper also proposed a solution for numerical errors and singularity issues. And showed the two proposed methods can perform well in revealing the significance of parameter in distributed datasets, comparing to a centralized GLMM algorithm from R package (‘lme4’) as the baseline model.

Methods
The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation, abbreviated as LA and GH), which supports federated decomposition of GLMM to bring computation to data. To solve the numerical errors and singularity issues, the loss-less estimation of log-sum-exponential trick and the adaptive regularization strategy was used to tackle the problems caused by federated settings.

Results
Our proposed method can handle GLMM to accommodate hierarchical data with multiple non-independent levels of observations in a federated setting. The experiment results demonstrate comparable (LA) and superior (GH) performances with simulated and real-world data.

Conclusion
We modified and compared federated GLMMs with different approximations, which can support researchers in analyzing versatile biomedical data to accommodate mixed effects and address non-independence due to hierarchical structures (i.e., institutes, region, country, etc.).