bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Tubulointerstitial Nephritis in a Patient on Anti-Programmed Death-Ligand 1 Triggered by COVID-19: A Case Report
Authors: Buyansky Dimitry , Fallaha Catherine , Gougeon François , Pépin Marie-Noëlle , Cailhier Jean-François , Beaubien-Souligny William 
Published: May 2021

Rationale: Immune checkpoint inhibitors are monoclonal antibodies used in the treatment of various types of cancers. The downside of using such molecules is the potential risk of developing immune-related adverse events. Factors that trigger these autoimmune side effects are yet to be elucidated. Although any organ can potentially be affected, kidney involvement is usually rare. In this case report, we describe the first known instance of a patient being treated with an inhibitor of programmed death-ligand 1 (anti-PD-L1, a checkpoint inhibitor) who develops acute tubulointerstitial nephritis after contracting the severe acute respiratory syndrome coronavirus 2. Presenting concerns of the patient: A 62-year-old patient, on immunotherapy treatment for stage 4 squamous cell carcinoma, presents to the emergency department with symptoms of lower respiratory tract infection. Severe acute kidney injury is discovered with electrolyte imbalances requiring urgent dialysis initiation. Further testing reveals that the patient has contracted the severe acute respiratory syndrome coronavirus 2. Diagnosis: A kidney biopsy was performed and was compatible with acute tubulointerstitial nephritis. Interventions: The patient was treated with high dose corticosteroid therapy followed by progressive tapering. Outcomes: Rapid and sustained normalization of kidney function was achieved after completion of the steroid course. Novel findings: We hypothesize that the viral infection along with checkpoint inhibitor use has created a proinflammatory environment which led to a loss of self-tolerance to renal parenchyma. Viruses may play a more important role in the pathogenesis of autoimmunity in this patient population than was previously thought.
Do Supply Chain Performance Influence Firm Profitability? A Predictive Approach in the Context of the Indian Pharmaceutical Industry
Authors: Tripathi Saswati , Talukder Bijoy , Rangarajan Krishnamachari 
Published: May 2021

The competitive nature of the pharmaceutical industry necessitates that its multifaceted supply-chain be cost-efficient and profitable. This paper aims to ascertain the critical supply-chain financial indicators influencing pharmaceutical-supply-chain (PSC) performance, revealing its unique features and assessing these indicators’ effect on profitability. This paper measures the PSC performance of 55 public-limited Indian pharmaceutical firms, including multinational enterprises, integrating supply-chain financial variables and SCOR KPIs through a ten-year timeline. The critical supply-chain-performance indicators (SCPIs) are identified from the measured set through factor analysis. A panel data random effect model is developed, linking these critical SCPIs and profitability to understand their significant influence on profitability. This paper has evidenced the existence of three critical SCPIs, revealing working capital efficiency, material flow efficiency and investment efficiency. It has also proved the significant influence of these SCPIs on firms’ profitability and has brought out the importance of material flow efficiency in terms of inventory and distribution efficiency as a leading contributing factor for profitability. This paper contributes to finding key PSC performance features and their vital role in pharmaceutical firms’ profitability. Supply-chain managers can enhance PSC’s specific performance areas to be cost-efficient and can increase the firm’s profitability.
Antibiotic Prophylaxis in Alloplastic Breast Reconstruction: Regimens and Outcomes
Authors: Liu Edward H. , Tong Mary , Kim Grace Y. , Farrokhyar Forough , Dal Cin Arianna 
Published: May 2021

Purpose: Surgical site infections (SSI) in prosthesis-based breast reconstruction can have a significant impact on patient outcome. Despite current CDC (Centers for Disease Control and Prevention) guidelines recommending 24 hours of postoperative antibiotics, various perioperative antimicrobial regimens are reported in the literature. Consensus on the optimal duration of antibiotics remains unclear. In this study, the aim is to compare the incidence of surgical site infections following different antibiotic durations in alloplastic breast reconstruction. Methods: In this retrospective cohort study, all consecutive patients who underwent expander/implant-based breast reconstruction between January 2009 and December 2014 at a tertiary centre were included. Data on patient demographics, risk factors, operative time, choice and timing of antibiotic used before surgery, and the duration of postoperative antibiotic use were collected. The primary outcome, SSI, is defined according to CDC criteria. Results: A total of 507 consecutive expander/implant-based cases were included. Minimum follow-up time was 1 year. The overall infection incidence was 14% (95% CI: 11%-17%), and the rate of subsequent explantation was 8%. Of the infected cases, 80% (45/56) received 1 week of postoperative antibiotic, while 20% (11/56) had a prolonged course of antibiotics (2-3 weeks; P = .003, odds ratio [OR] = 2.9; 95% CI: 1.4-5.8). Most infections were superficial (65%). Prior history of radiation treatment was identified as a risk factor for developing surgical site infection ( P = .02). Conclusion: Overall infection rate and risk factors for infections are in keeping with current literature. Prescribing one week of postoperative antibiotic was found to be associated with a higher incidence of SSI compared to a more prolonged antibiotic regimen.
Effect of Geographical Diversities in Management Leadership with Special Reference to India
Authors: Majumdar Soumen 
Published: May 2021

Effective top management leadership is the pillar of success in any organization. This is a widely shared view since the inception of industrial age. Though it is still valid in the current era, with the advancement of technology and workforce quality, leadership approaches are getting more sophisticated with every passing day. In today’s business context, success is no more associated with stereotyped leadership approaches. It is associated with the contingent approaches of leadership which are flexible and adaptive with varied socio-cultural aspects in different demographic regions. In this article, we focus on investigating how demographic factors influence the success or failure of top management leadership in the Indian context. In the course of our research, we considered seven different factors (availability of raw material, market demand for finished goods, proper utilization of equipment, manpower utilization, salaries and wages, uninterrupted availability of energy and fuel, and investment in technology) as key factors for the success of any manufacturing unit. Our findings indicate that, among these seven factors, only two (utilization of equipment and manpower utilization) are associated with the demographic aspects of a business operation. Even after handling five factors successfully, if the senior leadership fails to address the social, cultural and political issues of a certain demography, it leads to ineffective utilization of manpower. In addition to this, the leader’s inability in realizing the level of education, knowledge, and intelligence of the workforce of a specific demographic region can lead to inefficient machine utilization. These elucidations guided us to conclude our research by pointing out demographic factors as key considerations in the recruitment, selection, and placement process of top management leadership positions in any manufacturing unit across the country.
Core-binding factor leukemia hijacks the T-cell–prone PU.1 antisense promoter
Authors: van der Kouwe E. , Heller G. , Czibere A. , Pulikkan J. A. , Agreiter C. , Castilla L. H. , Delwel R. , Di Ruscio A. , Ebralidze A. K. , Forte M. , Grebien F. , Heyes E. , Kazianka L. , Klinger J. , Kornauth C. , Le T. , Lind K. , Barbosa I. A. M. , Pemovska T. , Pichler A. , Schmolke A.-S. , Schweicker C. M. , Sill H. , Sperr W. R. , Spittler A. , Surapally S. , Trinh B. Q. , Valent P. , Vanura K. , Welner R. S. , Zuber J. , Tenen D. G. , Staber P. B. 
Published: May 2021

AbstractThe blood system serves as a key model for cell differentiation and cancer. It is orchestrated by precise spatiotemporal expression of crucial transcription factors. One of the key master regulators in the hematopoietic systems is PU.1. Reduced levels of PU.1 are characteristic for human acute myeloid leukemia (AML) and are known to induce AML in mouse models. Here, we show that transcriptional downregulation of PU.1 is an active process involving an alternative promoter in intron 3 that is induced by RUNX transcription factors driving noncoding antisense transcription. Core-binding factor (CBF) fusions RUNX1-ETO and CBFβ-MYH11 in t(8;21) and inv(16) AML, respectively, activate the PU.1 antisense promoter that results in a shift from sense toward antisense transcription and myeloid differentiation blockade. In patients with CBF-AML, we found that an elevated antisense/sense transcript and promoter accessibility ratio represents a hallmark compared with normal karyotype AML or healthy CD34+ cells. Competitive interaction of an enhancer with the proximal or the antisense promoter forms a binary on/off switch for either myeloid or T-cell development. Leukemic CBF fusions thus use a physiological mechanism used by T cells to decrease sense transcription. Our study is the first example of a sense/antisense promoter competition as a crucial functional switch for gene expression perturbation by oncogenes. Hence, this disease mechanism reveals a previously unknown Achilles heel for future precise therapeutic targeting of oncogene-induced chromatin remodeling.
Toward prevention of childhood ALL by early-life immune training
Authors: Hauer Julia , Fischer Ute , Borkhardt Arndt 
Published: May 2021

AbstractB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common form of childhood cancer. Chemotherapy is associated with life-long health sequelae and fails in ∼20% of cases. Thus, prevention of leukemia would be preferable to treatment. Childhood leukemia frequently starts before birth, during fetal hematopoiesis. A first genetic hit (eg, the ETV6-RUNX1 gene fusion) leads to the expansion of preleukemic B-cell clones, which are detectable in healthy newborn cord blood (up to 5%). These preleukemic clones give rise to clinically overt leukemia in only ∼0.2% of carriers. Experimental evidence suggests that a major driver of conversion from the preleukemic to the leukemic state is exposure to immune challenges. Novel insights have shed light on immune host responses and how they shape the complex interplay between (1) inherited or acquired genetic predispositions, (2) exposure to infection, and (3) abnormal cytokine release from immunologically untrained cells. Here, we integrate the recently emerging concept of “trained immunity” into existing models of childhood BCP-ALL and suggest future avenues toward leukemia prevention.
Fabrication of Rectification Nanosensors by Direct Current Dielectrophoresis Alignment of ZnO Nanowires
Authors: Sun Kai-Heng , Chien Wen-Ching , Hsu Hsun-Feng 
Published: May 2021

AbstractThis work demonstrates the fabrication and characterization of ZnO nanowire-based devices in a metal–nanowire–metal configuration using the direct current dielectrophoresis alignment across Au electrodes. The current–voltage characteristics of the devices revealed that they were rectifying, and the direction of rectification was determined by the direction of current due to the asymmetric Joule heating in the dielectrophoresis alignment process. Joule heating caused the Au atoms to diffuse from the Au electrodes to the inner ZnO NWs and the formation of Schottky contact at the Au/ZnO interface. A fast and sensitive photoresponse was achieved for the rectifying devices in reverse-biased mode due to the carrier injection and photocurrent gain under UV illumination. Such direct current dielectrophoresis alignment of ZnO nanowires is a facile method for fabricating rectification devices with application in sensitive and fast UV detecting sensors.
Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis
Authors: Hsiao Chia-Chi , Teng Pai-Hsueh , Wu Yun-Ju , Shen Yi-Wen , Mar Guang-Yuan , Wu Fu-Zong 
Published: May 2021

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is associated with high risk of cardiovascular disease. The prevalence is increasing to 45–65% in the general population with routine health check-up, and most subjects have the mild degree NAFLD in recent years. Moreover, there are no studies on the association between NAFLD severity and coronary atherosclerosis in the real-world setting by ultrasonography.

Methods
The aim of this study was to determine the relationship between the severity of NAFLD and subclinical coronary atherosclerosis. Overall, 817 subjects meet criteria for NAFLD were enrolled in the retrospective cohort study (155 subjects were excluded). The severity of NAFLD was divided into the normal, mild, moderate and severe degree based on the finding of abdominal ultrasonography. The assessment of coronary atherosclerosis was based on CAC scan/coronary CT angiography finding in terms of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s).

Results
A significant linear trend was observed between the severity of NAFLD and subclinical coronary atherosclerosis. Compared with the reference group (including normal, mild, and moderate NAFLD), severe degree NAFLD was the independently associated risk of subclinical coronary atherosclerosis in term of CAC score ≧ 100, CAC score ≧ 400, CAD-RADS ≧ 3 and presence of vulnerable plaque(s) based on binary logistic regression after adjustment for FRS score and body fat percentage.

Conclusions
Severe degree, but not mild to moderate, was associated with high risk of subclinical coronary atherosclerosis, independently of FRS score and body-fat percentage.
Clinical features and outcomes of COVID-19 in older adults: a systematic review and meta-analysis
Authors: Singhal Sunny , Kumar Pramod , Singh Sumitabh , Saha Srishti , Dey Aparajit Ballav 
Published: May 2021

Abstract
Background
Few studies have focused on exploring the clinical characteristics and outcomes of COVID-19 in older patients. We conducted this systematic review and meta-analysis to have a better understanding of the clinical characteristics of older COVID-19 patients.

Methods
A systematic search of PubMed and Scopus was performed from December 2019 to May 3rd, 2020. Observational studies including older adults (age ≥ 60 years) with COVID-19 infection and reporting clinical characteristics or outcome were included. Primary outcome was assessing weighted pooled prevalence (WPP) of severity and outcomes. Secondary outcomes were clinical features including comorbidities and need of respiratory support.

Result
Forty-six studies with 13,624 older patients were included. Severe infection was seen in 51% (95% CI– 36-65%, I2–95%) patients while 22% (95% CI– 16-28%, I2–88%) were critically ill. Overall, 11% (95% CI– 5-21%, I2–98%) patients died. The common comorbidities were hypertension (48, 95% CI– 36-60% I2–92%), diabetes mellitus (22, 95% CI– 13-32%, I2–86%) and cardiovascular disease (19, 95% CI – 11-28%, I2–85%). Common symptoms were fever (83, 95% CI– 66-97%, I2–91%), cough (60, 95% CI– 50-70%, I2–71%) and dyspnoea (42, 95% CI– 19-67%, I2–94%). Overall, 84% (95% CI– 60-100%, I2–81%) required oxygen support and 21% (95% CI– 0-49%, I2–91%) required mechanical ventilation. Majority of studies had medium to high risk of bias and overall quality of evidence was low for all outcomes.

Conclusion
Approximately half of older patients with COVID-19 have severe infection, one in five are critically ill and one in ten die. More high-quality evidence is needed to study outcomes in this vulnerable patient population and factors affecting these outcomes.
Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them
Authors: de Laval Franck , Grosset-Janin Anaïs , Delon François , Allonneau Alexandre , Tong Christelle , Letois Flavie , Couderc Anne , Sanchez Marc-Antoine , Destanque César , Biot Fabrice , Raynaud Françoise , Bigaillon Christine , Ferraris Olivier , Simon-Loriere Etienne , Enouf Vincent , Andriamanantena Dinaherisoa , de Santi Vincent Pommier , Javelle Emilie , Mérens Audrey 
Published: May 2021

Abstract
Background
This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability.

Methods
The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88). One month later, we performed serology testing to test and screen symptomatic and asymptomatic cases again (n = 79).

Results
Twenty-four patients were confirmed (14 with RT-PCR and 10 with serology). The attack rate was 29% (24/83). Median age was 40 (24 to 59), and the sex ratio was 15/12. Only three cases were asymptomatic (= no symptoms at all, 13%, 95% CI, 3–32). Nineteen symptomatic cases (79%, 95% CI, 63–95) presented a respiratory infection, two of which were severe. All the RT-PCR confirmed cases acquired protective antibodies.
Median incubation was 4 days (from 1 to 13 days), and the median serial interval was 3 days (0 to 15). We identified pre-symptomatic transmission in 40% of this cluster, but no transmission from asymptomatic to symptomatic cases.

Conclusion
We report the effective use of targeted testing according to pre-test probability, specifically prioritizing symptomatic COVID-19 diagnosis and contact tracing. The asymptomatic rate raises questions about the real role of asymptomatic infected people in transmission. Conversely, pre-symptomatic contamination occurred frequently in this cluster, highlighting the need to identify, test, and quarantine asymptomatic at-risk contact persons (= contact tracing). The local lockdown imposed helped reduce transmission during the investigation period.
Hypertriglyceridemic waist phenotype and risk of chronic kidney disease in community-dwelling adults aged 60 years and older in Tianjin, China: a 7-year cohort study
Authors: Chen Ruping , Sun Guangshan , Liu Rui , Sun Ao , Cao Yujie , Zhou Xiaojie , Zhang Sha 
Published: May 2021

Abstract
Background
The hypertriglyceridemic waist (HTGW) phenotype has been proposed to be related to the occurrence and progression of chronic kidney disease (CKD). The ageing trend of the Chinese population continues to intensify, and elderly individuals are at high risk of CKD. The purpose of this study was to investigate the cross-sectional and longitudinal associations between the HTGW phenotype and the risk of CKD by following community-dwelling adults aged 60 years and older in Tianjin, China, for 7 years.

Methods
This study was an observational cohort study conducted between 2013 and 2019. Of 2050 participants aged 60 years and older who underwent an annual health examination in 2013, 1605 individuals with complete data were enrolled in the cross-sectional analysis. Among them, 1271 individuals were observed until 2019. Detailed follow-up records were available for 816 participants, of whom 600 participants without CKD at baseline were eligible for inclusion in the retrospective analysis. The HTGW phenotype was defined as a waist circumference of 90 cm or more and triglyceride concentrations of 2.0 mmol/L or more in males or a waist circumference of 85 cm or more and triglyceride concentrations of 1.5 mmol/L or more in females. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 and/or proteinuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g). Multivariable logistic regression analyses were performed to evaluate the relationship between the HTGW phenotype and CKD.

Results
In 2013, the prevalence of CKD among older adults was 31.03%, and the prevalence of CKD in the HTGW phenotype group was 37.81%. Over a 7-year observation period, 195 individuals developed CKD, with an incidence rate of 32.50%. Statistically significant associations were observed between the HTGW phenotype and CKD in older adults in both cross-sectional surveys and retrospective analyses, with odds ratios and 95% confidence intervals of 1.38 (95% CI: 1.03–1.86, P = 0.033) and 2.27 (95% CI: 1.30–3.97, P = 0.004), respectively, after adjustment for confounders.

Conclusions
In this community-based cohort study, the HTGW phenotype was confirmed to be independently associated with an increased risk of prevalent and incident CKD in older adults aged 60 years and above in Tianjin, China.
Metabolic acidosis is associated with increased risk of adverse kidney outcomes and mortality in patients with non-dialysis dependent chronic kidney disease: an observational cohort study
Authors: Tangri Navdeep , Reaven Nancy L. , Funk Susan E. , Ferguson Thomas W. , Collister David , Mathur Vandana 
Published: May 2021

Abstract
Background
Management of chronic kidney disease (CKD) requires the management of risk factors, such as hypertension and albuminuria, that affect CKD progression. Identification of additional modifiable risk factors is necessary to develop new treatment strategies for CKD. We sought to quantify the association of metabolic acidosis with CKD progression and mortality in a large U.S. community-based cohort.

Methods
In this longitudinal, retrospective cohort study we identified non-dialysis-dependent patients with stage 3‒5 CKD from Optum’s de-identified integrated electronic health records. We selected cohorts of patients with confirmed metabolic acidosis or normal serum bicarbonate levels based on 2 consecutive serum bicarbonate values: 12 to < 22 mEq/L or 22-29 mEq/L, respectively, 28‒365 days apart. The primary composite outcome was ≥ 40 % decline in estimated glomerular filtration rate (eGFR), renal replacement therapy (chronic dialysis or kidney transplant), or all-cause mortality (DD40). Secondary outcomes included each component of the composite outcome. Cox proportional hazards models were used for the DD40 outcome and secondary outcomes, while logistic regression models were used for the DD40 outcome at 2 years.

Results
A total of 51,558 patients qualified for the study. The unadjusted 2-year incidence of adverse renal and fatal outcomes was significantly worse among patients in the metabolic acidosis group vs. those who had normal serum bicarbonate levels: 48 % vs. 17 % for DD40, 10 % vs. 4 % for ≥ 40 % decline in eGFR, 20 % vs. 6 % for renal replacement therapy, and 31 % vs. 10 % for all-cause mortality (all P < 0.001). Over a ≤ 10-year period, for each 1-mEq/L increase in serum bicarbonate, the adjusted hazard ratio for DD40 was 0.926 (95 % confidence interval [CI], 0.922–0.930; P < 0.001); over a ≤ 2-year period, the adjusted odds ratio for DD40 was 0.873 (95 % CI, 0.866–0.879; P < 0.001).

Conclusions
In this large community cohort of patients with stage 3‒5 CKD, the presence of metabolic acidosis was a significant, independent risk factor for the composite adverse outcome of CKD progression, renal replacement therapy, and all-cause mortality (DD40).