bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Quality Improvement Study of Insulin-Induced Hypoglycemia and Implementation of Hospital-Wide Initiatives
Authors: Shelton Carter , Demidowich Andrew P. , Motevalli Mahsa , Sokolinsky Sam , MacKay Periwinkle , Tucker Cynthia , Abundo Cora , Peters Eileen , Gooding Roliette , Hackett Margaret , Wedler Joyce , Alexander Lee Ann , Barry Luvenia , Flynn Mary , Rios Patricia , Fulda Constance Lulu , Young Michelle F. , Kahl Barbara , Pummer Eileen , Mathioudakis Nestoras N. , Sidhaye Aniket , Howell Eric E. , Rotello Leo , Zilbermint Mihail 
Published: April 2021

Background: Hospitalized patients who are receiving antihyperglycemic agents are at increased risk for hypoglycemia. Inpatient hypoglycemia may lead to increased risk for morbidity, mortality, prolonged hospitalization, and readmission within 30 days of discharge, which in turn may lead to increased costs. Hospital-wide initiatives targeting hypoglycemia are known to be beneficial; however, their impact on patient care and economic measures in community nonteaching hospitals are unknown. Methods: This retrospective quality improvement study examined the effects of hospital-wide hypoglycemia initiatives on the rates of insulin-induced hypoglycemia in a community hospital setting from January 1, 2016, until September 30, 2019. The potential cost of care savings has been calculated. Results: Among 49 315 total patient days, 2682 days had an instance of hypoglycemia (5.4%). Mean ± SD hypoglycemic patient days/month was 59.6 ± 16.0. The frequency of hypoglycemia significantly decreased from 7.5% in January 2016 to 3.9% in September 2019 ( P = .001). Patients with type 2 diabetes demonstrated a significant decrease in the frequency of hypoglycemia (7.4%-3.8%; P < .0001), while among patients with type 1 diabetes the frequency trended downwards but did not reach statistical significance (18.5%-18.0%; P = 0.08). Based on the reduction of hypoglycemia rates, the hospital had an estimated cost of care savings of $98 635 during the study period. Conclusions: In a community hospital setting, implementation of hospital-wide initiatives targeting hypoglycemia resulted in a significant and sustainable decrease in the rate of insulin-induced hypoglycemia. These high-leverage risk reduction strategies may be translated into considerable cost savings and could be implemented at other community hospitals.
Clinical Validity of 3 Different Grading Systems for Facet Joint Violation: A Retrospective Study and In-Depth Review
Authors: Zhao Yiwei , Yuan Suomao , Liu Wubo , Tian Yonghao , Liu Xinyu 
Published: April 2021

Study Design: Retrospective. Objectives: To study the violation rate of 3 different types of facet joint violation (FJV) grading systems (Babu, Shah, and Park), and to evaluate the accuracy, reliability, and association with clinical outcomes of the above 3 grading systems. Methods: 152 patients of lumbar spinal stenosis treated with percutaneous pedicle screw placement were enrolled in our study. FJV was evaluated on 3-dimensional lumbar CT reconstruction. Three types of grading systems were used to evaluate FJV: Babu’s system (grading by the severity of violation), Shah’s system (grading by side of violation), and modified Park’s system (grading by different components to cause violation). The violation rate and observer consistency of the 3 grading systems were analyzed. Clinical outcomes were evaluated by visual analog score (VAS), Oswestry disability index (ODI) score. Results: Kappa coefficients of interobserver consistency on Babu, Shah, and Park grading systems were 0.726,0.849,0.692, respectively. The violation rate of Babu, Shah, and Park grading systems were comparable, which were 34.54%, 32.57%, 33.55%, respectively. In all 3 grading systems, the postoperative VAS low-back pain and ODI scores in non-FJV groups were lower than those in FJV groups ( P < .05), and there were no significant differences between 2 groups in VAS leg pain( P >.05). Conclusions: Babu, Shah and modified Park grading system are reliable grading systems, and it reported comparable violation rate. The self-reported clinical outcomes of patients with FJV were worse at 2-year follow-up. For clinical application, it is recommended to use 2 or even 3 different grading systems together to evaluate the FJV.
New Grading System for Cervical Paraspinal Soft Tissue Damage After Traumatic Cervical Spinal Cord Injury Without Major Fracture Based on the Short-T1 Inversion Recovery Mid-Sagittal MRI for Prediction of Neurological Improvements: The STIR-MRI Grade
Authors: Aburakawa Kotaro , Yokoyama Toru , Takeuchi Kazunari , Numasawa Takuya , Wada Kanichiro , Kumagai Gentaro , Tanaka Sunao , Asari Toru , Otsuka Hironori , Ishibashi Yasuyuki 
Published: April 2021

Study Design: Retrospective cohort study. Objective: To develop a grading method for cervical paraspinal soft tissue damage after cervical spinal cord injury (CSCI) without major fracture based on the short T1 inversion recovery (STIR) mid-sagittal magnetic resonance image (MRI) for prediction of neurological improvements. Methods: This study included 34 patients with CSCI without major fracture, treated conservatively for at least 1 year and graded using the STIR-MRI Grade. This system consists of anterior grades; A0: no high-intensity area (HIA), A1: linear HIA, and A2: fusiform HIA, and posterior grades; P0: no HIA, P1: HIA not exceeding the nuchal ligament, and P2: HIA exceeding the nuchal ligament, within 24 hours postinjury. The American Spinal Injury Association impairment scale (AIS) and the Japanese Orthopedic Association (JOA) scores were examined. Results: Anterior grades were not significantly correlated with the AIS and JOA score. At both injury and final follow-up, the AIS in P2 patients was significantly more severe ( P = 0.007, P = 0.015, respectively) than that in P0 patients. At the injury, the AIS in P2 patients was significantly more severe ( P = 0.008) than that in P1 patients. Among P2 patients only, the JOA score at the injury (1.4 points) did not improve by the final follow-up (3.9 points). The final follow-up JOA score (3.9 points) in P2 patients was significantly lower than that (13.6 points) in P0 patients ( P = 0.016). Conclusions: Grade P2 led to poor neurological outcomes. The STIR-MRI Grade is a prognostic indicator for neurological improvements past-CSCI.
Lenalidomide triggers T-cell effector functions in vivo in patients with follicular lymphoma
Authors: Ménard Cédric , Rossille Delphine , Dulong Joelle , Nguyen Tien-Tuan , Papa Ilenia , Latour Maelle , Bescher Nadège , Bezier Isabelle , Chouteau Myriam , Fest Thierry , Houot Roch , Morschhauser Franck , Tarte Karin 
Published: April 2021

Abstract
The immunomodulatory drug lenalidomide is used in patients with follicular lymphoma (FL) with the aim of stimulating T-cell antitumor immune response. However, little is known about the effects of lenalidomide on T-cell biology in vivo in patients with FL. We thus undertook an extensive longitudinal immunologic study, including phenotypic, transcriptomic, and functional analyses, on 44 first-line and 27 relapsed/refractory patients enrolled in the GALEN trial (Obinutuzumab Combined With Lenalidomide for Relapsed or Refractory Follicular B-Cell Lymphoma) to test the efficacy of lenalidomide and obinutuzumab combination in patients with FL. Lenalidomide rapidly and transiently induced an activated T-cell phenotype, including HLA-DR, Tim-3, CD137, and programmed cell death protein 1 (PD-1) upregulation. Furthermore, sequential RNA-sequencing of sorted PD-1+ and PD-1– T-cell subsets revealed that lenalidomide triggered a strong enrichment for several gene signatures related to effector memory T-cell features, including proliferation, antigen receptor signaling, and immune synapse restoration; all were validated at the phenotypic level and with ex vivo functional assays. Correlative analyses pinpointed a negative clinical impact of high effector T-cell and regulatory T-cell percentages before and during treatment. Our findings bring new insight in lenalidomide mechanisms of action at work in vivo and will fuel a new rationale for the design of combination therapies.
Molecular Dynamics Simulation on Cutting Mechanism in the Hybrid Machining Process of Single-Crystal Silicon
Authors: Liu Changlin , He Wenbin , Chu Jianning , Zhang Jianguo , Chen Xiao , Xiao Junfeng , Xu Jianfeng 
Published: April 2021

AbstractIn this paper, molecular dynamics simulations are carried out to investigate the cutting mechanism during the hybrid machining process combined the thermal and vibration assistants. A modified cutting model is applied to study the material removal behavior and subsurface damage formation in one vibration cycle. The results indicate that during the hybrid machining process, the dominant material removal mechanism could transform from extrusion to shearing in a single vibration cycle. With an increase of the cutting temperature, the generation and propagation of cracks are effectively suppressed while the swelling appears when the dominant material removal mechanism becomes shearing. The formation mechanism of the subsurface damage in one vibration cycle can be distinct according to the stress distribution. Moreover, the generation of the vacancies in workpiece becomes apparent with increasing temperature, which is an important phenomenon in hybrid machining process.
Fulminant hepatic failure in a patient testing re-positive for SARS-CoV-2: a case report
Authors: Aldossary Bader , Hassan Ali , Moussa Mohamed , Alsaif Hind S. , Alfaraj Dunya 
Published: April 2021

Abstract
Background
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not elicit lifelong protective immunity and reinfection could occur. Liver function impairment is a common manifestation of coronavirus disease 2019 (COVID-19). However, acute hepatic failure in the setting of COVID-19 is very rare.

Case presentation
We report the case of a 47-year-old woman who presented with acute abdominal pain and vomiting. Abdominal examination revealed a soft and lax abdomen with mild tenderness in the right upper quadrant. The patient recovered from COVID-19 2 months previously with negative results on reverse transcription-polymerase chain reaction (RT-PCR). Laboratory investigations revealed markedly elevated transaminases with normal results on viral hepatitis serology panel and undetectable blood paracetamol level. Prior to admission, the patient underwent RT-PCR for SARS-CoV-2, which revealed a positive result. The patient experienced rapid deterioration in the neurological status with a remarkable increase in the liver enzyme levels. Despite aggressive resuscitation, the patient suffered irreversible cardiac arrest and died.

Conclusion
Fulminant hepatic failure is a rare manifestation in patients with re-positive RT-PCR tests for SARS-CoV-2. Clinicians should maintain a high index of suspicion for hepatic injury with active monitoring of liver enzymes.
Association of vitamin D pathway genes polymorphisms with pulmonary tuberculosis susceptibility in a Chinese population
Authors: Zhang Tian-Ping , Chen Shuang-Shuang , Zhang Gen-You , Shi Si-Jiu , Wei Li , Li Hong-Miao 
Published: April 2021

Abstract
Objective
This study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) of vitamin D metabolic pathway genes with susceptibility to pulmonary tuberculosis (PTB).

Methods
Nine hundred seventy-nine patients (490 PTB cases and 489 healthy controls) were included in this study. Seventeen SNPs of vitamin D metabolic pathway genes, including CYP24A1, CYP27A1, CYP27B1, CYP2R1, GC, and DHCR7, were genotyped with improved multiple ligase detection reaction (iMLDR).

Results
The GC rs3733359 GA, rs16847024 CT genotypes were significantly associated with the reduced risk of PTB, and the rs3733359 A, rs16847024 T alleles were also associated with the decreased PTB susceptibility. The GT genotype of GC rs4588 variant was significantly higher in patients with PTB when compared to controls. Moreover, the increased risk of rs3733359 and rs16847024 variants, and a decreased risk of rs4588, were found under the dominant mode among the PTB patients. However, there was no significant relationship of CYP24A1, CYP27A1, CYP27B1, CYP2R1, and DHCR7 polymorphisms with the risk of PTB. In CYP27A1, the rs17470271 T and rs933994 T alleles were significantly associated with leukopenia, drug resistance in the PTB patients, respectively. In GC gene, the rs7041 and rs3733359 variants were found to be associated with pulmonary infection, fever in the PTB patients, respectively. The increased frequency of rs16847024 TT genotype was found in the PTB patients with fever and drug-induced liver damage. DHCR7 rs12785878 TT genotype, and T allele frequencies were both significantly associated with pulmonary infection in the PTB patients. The haplotype analysis showed that CYP24A1 TACT, CYP2R1 GGCT, GGAT, GC AATG haplotypes were related to PTB susceptibility.

Conclusion
Our study suggested that GC SNPs were associated with the genetic background of PTB. CYP27A1, GC, and DHCR7 genetic variations might contribute to several clinical phenotypes of PTB in Chinese.
Dynamics of rumen gene expression, microbiome colonization, and their interplay in goats
Authors: Pan Xiangyu , Li Zongjun , Li Bibo , Zhao Chen , Wang Yu , Chen Yulin , Jiang Yu 
Published: April 2021

Abstract
Background
Preweaned rumen development is vital for animal health and efficient fermentation. In this study, we integrated ruminal transcriptomic and metagenomic data to explore the dynamics of rumen functions, microbial colonization, and their functional interactions during the first 8 weeks of life in goats.

Results
The dynamic rumen transcriptomic and microbial profiles both exhibited two distinct phases during early rumen development. The differentially expressed genes of the rumen transcriptome between the two phases showed that the immune-related response was enriched in the first phase and nutrient-related metabolism was enriched in the second phase, whereas the differentially expressed genes of the rumen microbiome were enriched in bacteriocin biosynthesis and glycolysis/gluconeogenesis activities. The developmental shift in the rumen transcriptome (at d 21) was earlier than the feed stimulus (at d 25) and the shift in the rumen microbiome (at d 42). Additionally, 15 temporal dynamic rumen gene modules and 20 microbial modules were revealed by coexpression network analysis. Functional correlations between the rumen and its microbiome were primarily involved in rumen pH homeostasis, nitrogen metabolism and the immune response. Rumen gene modules associated with the microbial alpha diversity index were also enriched in the immune response process.

Conclusions
The present study touched the critical developmental process of rumen functions, microbial colonization and their functional interactions during preweaned development. Taken together, these results demonstrated that rumen development at the first phase is more likely a programmed process rather than stimulation from feed and the microbiome, while the shift of rumen metagenomes was likely regulated by both the diet and host. The intensive functional correlations between rumen genes and the microbiome demonstrated that synergistic processes occurred between them during early rumen development.
Genetic variability in multidrug-resistant Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in North India
Authors: Singh Ajay Vir , Singh Suman , Yadav Anjali , Kushwah Shweta , Yadav Rajbala , Sai Davuluri Kushma , Chauhan Devendra Singh 
Published: April 2021

Abstract
Background
Information on the genetic variability of drug resistant isolates of Mycobacterium tuberculosis is of paramount importance to understand transmission dynamics of disease and to improve TB control strategies. Despite of largest number of multidrug-resistant (MDR) tuberculosis cases (1, 30,000; 27% of the global burden), strains responsible for the expansion or development of drug-resistant Mycobacterium tuberculosis infections have been poorly characterized in India. Present study was aimed to investigate the genetic diversity in MDR isolates of Mycobacterium tuberculosis in North India.

Results
Spacer oligonucleotide typing (spoligotyping) was performed on 293 clinical MDR isolates of Mycobacterium tuberculosis recovered from cases of pulmonary tuberculosis from North India. Spoligotyping identified 74 distinct spoligotype patterns. Comparison with an international spoligotype database (spoldb4 database) showed that 240 (81.91%) and 32 (10.92%) strains displayed known and shared type patterns, while 21 (7.16%) strains displayed unique spoligotype patterns. Among the phylogeographic lineages, lineage 3 (East African-Indian) was found most predominant lineage (n = 159, 66.25%), followed by lineage 2 (East Asian; n = 34, 14.16%), lineage 1 (Indo-Oceanic; n = 30, 12.50%) and lineage 4 (Euro American; n = 17, 7.08%). Overall, CAS1_DEL (60.41%; SITs 2585, 26, 2694, 309, 381, 428, 1401, 141, 25, 1327) was found most pre-dominant spoligotype pattern followed by Beijing (14.16%; SITs255, 260, 1941, 269) and EAI3_IND (5.00%; SITs 298, 338, 11). The demographic and clinical characteristics were not found significantly associated with genotypic lineages of MDR-M.tuberculosis isolates recovered from pulmonary TB patients of North India.

Conclusions
Present study reveals high genetic diversity among the Mycobacterium tuberculosis isolates and highlights that SIT141/CAS1_Del followed by SIT26/ Beijing lineage is the most common spoligotype responsible for the development and transmission of MDR-TB in North India. The high presence of shared type and unique spoligotype patterns of MDR strains indicates epidemiological significance of locally evolved strains in ongoing transmission of MDR-TB within this community which needs to be further monitored using robust molecular tools with high discriminatory power.
Clonal diversity and genomic characterization of Panton-valentine Leukocidin (PVL)-positive Staphylococcus aureus in Tehran, Iran
Authors: Najafi olya Zahra , Najar-Peerayeh Shahin , Yadegar Abbas , Bakhshi Bita 
Published: April 2021

Abstract
Background
Some Staphylococcus aureus strains produce Panton-Valentine leukocidin (PVL), a bi-component pore-forming toxin, which causes leukocyte lysis and tissue necrosis. Currently, there is very limited information on the molecular epidemiology of PVL-encoding S. aureus strains in Iran. This study aimed to determine the molecular epidemiology and genetic background of PVL-positive S. aureus clinical strains isolated from Iranian patients.

Methods
A total of 28 PVL-positive S. aureus strains were detected from 600 S. aureus isolates between February 2015 and March 2018 from different hospitals in Tehran, Iran. Antimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Molecular genotyping was performed using SCCmec and accessory gene regulator (agr) typing, PVL haplotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE).

Results
The highest antibiotic resistance rate was found to be against erythromycin (57.1%), followed by ciprofloxacin (42.8%) and clindamycin (35.7%). Moreover, 19 (67.9%) out of 28 S. aureus isolates were identified as MRSA, including CA-MRSA (14/19, 73.7%) and HA-MRSA (5/19, 26.3%). SCCmec type IVa was detected as the predominant type (10/19, 52.6%), followed by type III (5/19, 26.3%) and type V (4/19, 21.1%). The agr type I was identified as the most common type (14/28, 50%), and H and R haplotype groups were observed at frequencies of 67.9 and 32.1%, respectively. Among H variants, the predominant variant was H2 (78/9%). The isolates encompassed 21 different sequence types (STs), including 16 new STs (ST5147 to ST5162). Based on eBURST analysis, the isolates were clustered into five CCs, including CC30, CC22, CC1, CC8, and CC5 (ST5160), and nine singletons. PFGE typing showed that 24 isolates were clustered into A (4 pulsotypes), B (9 pulsotypes), and C (11 pulsotypes) clusters.

Conclusions
A high prevalence of PVL-positive CA-MRSA strains was detected in Iran. The majority of PVL-positive isolates were of H (mostly H2) variant, while R variant was harbored by 100% of PVL-positive MRSA strains. Also, CC8, CC22, and CC30 were identified as the dominant clones among PVL-encoding S. aureus strains. This study promotes a better understanding of the molecular epidemiology and evolution of PVL-positive S. aureus strains in Iran.
A composite biomarker of neutrophil-lymphocyte ratio and hemoglobin level correlates with clinical response to PD-1 and PD-L1 inhibitors in advanced non-small cell lung cancers
Authors: Ayers Kristin L. , Ma Meng , Debussche Gaspard , Corrigan David , McCafferty Jonathan , Lee Kyeryoung , Newman Scott , Zhou Xiang , Hirsch Fred R. , Mack Philip C. , Liu Jane J. , Schadt Eric E. , Chen Rong , Li Shuyu D. 
Published: April 2021

Abstract
Background
Immune checkpoint inhibitors (ICIs) have been incorporated into various clinical oncology guidelines for systemic treatment of advanced non-small cell lung cancers (aNSCLC). However, less than 50% (and 20%) of the patients responded to the therapy as a first (or second) line of therapy. PD-L1 immunohistochemistry (IHC) is an extensively studied biomarker of response to ICI, but results from this test have equivocal predictive power. In order to identify other biomarkers that support clinical decision-making around whether to treat with ICIs or not, we performed a retrospective study of patients with aNSCLC who underwent ICI-based therapy in the Mount Sinai Health System between 2014 and 2019.

Methods
We analyzed data from standard laboratory tests performed in patients as a part of the routine clinical workup during treatment, including complete blood counts (CBC) and a comprehensive metabolic panel (CMP), to correlate test results with clinical response and survival.

Results
Of 11,138 NSCLC patients identified, 249 had been treated with ICIs. We found associations between high neutrophil-to-lymphocyte ratio (NLR ≥ 5) and poor survival in ICI-treated NSCLC. We further observed that sustained high NLR after initiation of treatment had a more profound impact on survival than baseline NLR, regardless of PD-L1 status. Hazard ratios when comparing patients with NLR ≥ 5 vs. NLR < 5 are 1.7 (p = 0.02), 3.4 (p = 4.2 × 10− 8), and 3.9 (p = 1.4 × 10− 6) at baseline, 2–8 weeks, and 8–14 weeks after treatment start, respectively. Mild anemia, defined as hemoglobin (HGB) less than 12 g/dL was correlated with survival independently of NLR. Finally, we developed a composite NLR and HGB biomarker. Patients with pretreatment NLR ≥ 5 and HGB < 12 g/dL had a median overall survival (OS) of 8.0 months (95% CI 4.5–11.5) compared to the rest of the cohort with a median OS not reached (95% CI 15.9-NE, p = 1.8 × 10− 5), and a hazard ratio of 2.6 (95% CI 1.7–4.1, p = 3.5 × 10− 5).

Conclusions
We developed a novel composite biomarker for ICI-based therapy in NSCLC based on routine CBC tests, which may provide meaningful clinical utility to guide treatment decision. The results suggest that treatment of anemia to elevate HGB before initiation of ICI therapy may improve patient outcomes or the use of alternative non-chemotherapy containing regimens.