bluuebunny/crossref_metadata_2025 huggingface dataset:
Overtreatment in nonmalignant lesions detected in a colorectal cancer screening program: a retrospective cohort study
Authors: Cubiella Joaquín , González Antía , Almazán Raquel , Rodríguez-Camacho Elena , Zubizarreta Raquel , Peña-Rey Lorenzo Isabel
Published: July 2021

Background

Although colorectal cancer (CRC) screening programs reduce CRC incidence and mortality, they are associated with risks in healthy subjects. However, the risk of overtreatment and overdiagnosis has not been determined yet. The aim of this study was to report the surgery rates in patients with nonmalignant lesions detected within the first round of a fecal immunochemical test (FIT) based CRC screening program and the factors associated with it.

Methods

We included in this analysis all patients with nonmalignant lesions detected between May 2013 and June 2019 in the Galician (Spain) CRC screening program. We calculated surgery rate according to demographic variables, the risk classification according to the colonoscopy findings (European guidelines for quality assurance), the endoscopist’s adenoma detection rate (ADR) classified into quartiles and the hospital’s complexity level. We determined which variables were independently associated with surgery rate and expressed the association as Odds Ratio and its 95% confidence interval (CI).

Results

We included 15,707 patients in the analysis with high (19.9%), intermediate (26.9%) low risk (23.3%) adenomas and normal colonoscopy (29.9%) detected in the analyzed period. Colorectal surgery was performed in 162 patients (1.03, 95% CI 0.87–1.19), due to colonoscopy complications (0.02, 95% CI 0.00–0.05) and resection of colorectal benign lesions (1.00, 95% CI 0.85–1.16). Median hospital stay was 6 days with 17.3% patients developing minor complications, 7.4% major complications and one death. After discharge, complications developed in 18.4% patients. In benign lesions, an endoscopic resection was performed in 25.4% and a residual premalignant lesion was detected in 89.9%. The variables independently associated with surgery in the multivariable analysis were age (≥60 years = 1.57, 95% CI 1.11–2.23), sex (female = 2.10, 95% CI 1.52–2.91), the European guidelines classification (high risk = 67.94, 95% CI 24.87–185.59; intermediate risk = 5.63, 95% CI 1.89–16.80; low risk = 1.43; 95% CI 0.36–5.75), the endoscopist’s ADR (Q4 = 0.44, 95% CI 0.28–0.68; Q3 = 0.44, 95% CI 0.27–0.71; Q2 = 0.71, 95% CI 0.44–1.14) and the hospital (tertiary = 0.54, 95% CI 0.38–0.79).

Conclusions

In a CRC screening program, the surgery rate and the associated complications in patients with nonmalignant lesions are low, and related to age, sex, endoscopic findings, endoscopist’s ADR and the hospital’s complexity.
Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery
Authors: Chan Minhui Amy , Ibrahim Farah , Kumaran Arjunan , Yong Kailing , Chan Anita Sook Yee , Shen Sunny
Published: July 2021

Background

To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects.

Methods

Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA).

Results

There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334–0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were − 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively.

Conclusions

No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.
Effects of backhand stroke styles on bone mineral content and density in postmenopausal recreational tennis players: a cross-sectional pilot investigation
Authors: Wang Ho-Seng , Tsai Yi-Shan , Chen Yung-Chih , Chao Hsiao-Han , Lin Hsin-Shih , Chiang Yi-Pin , Chen Hou-Yu
Published: July 2021

Background

One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players.

Methods

BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers’ group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA.

Results

TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p < 0.05). Both OB and TB showed greater BMD inter-trochanter than SG (both, p < 0.05). OB demonstrated greater inter-arm differences in the distal radius, which involved 1/3 distal for BMC and mid-distal radius for BMD compared to the TB and SG (all, p < 0.05). In addition, greater inter-arm asymmetry of grip strength was found in OB compared to TB and SG (both, p < 0.05).

Conclusion

For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.
Measurement of empathy among health professionals during Syrian crisis using the Syrian empathy scale
Authors: Dashash Mayssoon , Boubou Mounzer
Published: July 2021

Background

Health professionals should have certain degree of empathy to eliminate the pain and suffering of their patients. There is a need to design a scale, which can assess empathy among health professionals and is relevant to community and culture. Therefore, this study was undertaken to measure the empathy among Syrian health professionals and students of health professions using a newly designed Syrian Empathy Scale that is relevant to community during Syrian crisis.

Methods

A cross-sectional observational study was undertaken. A total of 214 participants (118 males and 96 females) responded to the Syrian Empathy Scale SES from Medical (n = 62), Dental (n = 152). They were 59 undergraduates, 116 postgraduates and 39 general practitioners. The SES was designed as a tool that includes 20 items in a 7-point Likert-type scale with overall score ranges from 20 to 140. Group comparisons of the empathy scores were conducted using t-test and analysis of variance (ANOVA). A factor analysis was performed. Bartlett’s test of the sphericity and the KMO measure of sampling adequacy were also determined. Cronbach’s alpha was calculated.

Results

A significant difference was found between males and females in the SES mean score. The ANOVA analysis showed that the SES empathy scores of dentists were higher than the SES empathy scores in medical doctors with no significant difference. The SES empathy score of undergraduates was significantly higher than postgraduates and practitioners. Findings of KMO indicated sampling adequacy (KMO = 0.824 > 0.7) and the value of Bartlett’s test of the sphericity (1255.65, df = 190, P-value< 0.001) proved that the factor analysis is meaningful and acceptable. The results of varimax rotation proved that five main factors were retained.

Conclusion

Findings of this study support the reliability of the newly designed Syrian Empathy Scale for measuring empathy in the field of health care. The SES can be suggested for assessing empathy in different health educational programs. However, future works are still essential to support the validity of the scale as well as to ascertain the role of empathy in improving health care.
Health care ethics programs in U.S. Hospitals: results from a National Survey
Authors: Danis Marion , Fox Ellen , Tarzian Anita , Duke Christopher C.
Published: July 2021

Background

As hospitals have grown more complex, the ethical concerns they confront have grown correspondingly complicated. Many hospitals have consequently developed health care ethics programs (HCEPs) that include far more than ethics consultation services alone. Yet systematic research on these programs is lacking.

Methods

Based on a national, cross-sectional survey of a stratified sample of 600 US hospitals, we report on the prevalence, scope, activities, staffing, workload, financial compensation, and greatest challenges facing HCEPs.

Results

Among 372 hospitals whose informants responded to an online survey, 97% of hospitals have HCEPs. Their scope includes clinical ethics functions in virtually all hospitals, but includes other functions in far fewer hospitals: ethical leadership (35.7%), regulatory compliance (29.0%), business ethics (26.2%), and research ethics (12.6%). HCEPs are responsible for providing ongoing ethics education to various target audiences including all staff (77.0%), nurses (59.9%), staff physicians (49.0%), hospital leadership (44.2%), medical residents (20.3%) and the community/general public (18.4%). HCEPs staff are most commonly involved in policy work through review of existing policies but are less often involved in development of new policies. HCEPs have an ethics representative in executive leadership in 80.5% of hospitals, have representation on other hospital committees in 40.7%, are actively engaged in community outreach in 22.6%, and lead large-scale ethics quality improvement initiatives in 17.7%. In general, major teaching hospitals and urban hospitals have the most highly integrated ethics programs with the broadest scope and greatest number of activities. Larger hospitals, academically affiliated hospitals, and urban hospitals have significantly more individuals performing HCEP work and significantly more individuals receiving financial compensation specifically for that work. Overall, the most common greatest challenge facing HCEPs is resource shortages, whereas underutilization is the most common greatest challenge for hospitals with fewer than 100 beds. Respondents’ strategies for managing challenges include staff training and additional funds.

Conclusions

While this study must be cautiously interpreted due to its limitations, the findings may be useful for understanding the characteristics of HCEPs in US hospitals and the factors associated with these characteristics. This information may contribute to exploring ways to strengthen HCEPs.
Enforcing ATP hydrolysis enhanced anaerobic glycolysis and promoted solvent production in Clostridium acetobutylicum
Authors: Dai Zongjie , Zhu Yan , Dong Hongjun , Zhao Chunhua , Zhang Yanping , Li Yin
Published: July 2021

Background

The intracellular ATP level is an indicator of cellular energy state and plays a critical role in regulating cellular metabolism. Depletion of intracellular ATP in (facultative) aerobes can enhance glycolysis, thereby promoting end product formation. In the present study, we examined this s trategy in anaerobic ABE (acetone-butanol-ethanol) fermentation using Clostridium acetobutylicum DSM 1731.

Results

Following overexpression of atpAGD encoding the subunits of water-soluble, ATP-hydrolyzing F1-ATPase, the intracellular ATP level of 1731(pITF1) was significantly reduced compared to control 1731(pIMP1) over the entire batch fermentation. The glucose uptake was markedly enhanced, achieving a 78.8% increase of volumetric glucose utilization rate during the first 18 h. In addition, an early onset of acid re-assimilation and solventogenesis in concomitant with the decreased intracellular ATP level was evident. Consequently, the total solvent production was significantly improved with remarkable increases in yield (14.5%), titer (9.9%) and productivity (5.3%). Further genome-scale metabolic modeling revealed that many metabolic fluxes in 1731(pITF1) were significantly elevated compared to 1731(pIMP1) in acidogenic phase, including those from glycolysis, tricarboxylic cycle, and pyruvate metabolism; this indicates significant metabolic changes in response to intracellular ATP depletion.

Conclusions

In C. acetobutylicum DSM 1731, depletion of intracellular ATP significantly increased glycolytic rate, enhanced solvent production, and resulted in a wide range of metabolic changes. Our findings provide a novel strategy for engineering solvent-producing C. acetobutylicum, and many other anaerobic microbial cell factories.
Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers
Authors: He Yuting , Yu Xiao , Zhang Menggang , Guo Wenzhi
Published: July 2021

Background

5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs.

Methods

Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers.

Results

After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival.

Conclusion

Our results offered strong evidence and clinical implications for the involvement of m5C regulators.
Lower response to BNT162b2 vaccine in patients with myelofibrosis compared to polycythemia vera and essential thrombocythemia
Authors: Pimpinelli Fulvia , Marchesi Francesco , Piaggio Giulia , Giannarelli Diana , Papa Elena , Falcucci Paolo , Spadea Antonio , Pontone Martina , Di Martino Simona , Laquintana Valentina , La Malfa Antonia , Di Domenico Enea Gino , Di Bella Ornella , Falzone Gianluca , Ensoli Fabrizio , Vujovic Branka , Morrone Aldo , Ciliberto Gennaro , Mengarelli Andrea
Published: July 2021

In a population of 42 Philadelphia negative myeloproliferative neoplasm patients, all on systemic active treatment, the likelihood of responding to anti-SARS-CoV-2 BNT162b2 vaccine at 2 weeks after the second dose was significantly lower in the ten patients with myelofibrosis compared to the 32 with essential thrombocythemia (n = 17) and polycythemia vera (n = 15) grouped together, both in terms of neutralizing anti-SARS-CoV-2 IgG titers and seroprotection rates (32.47 AU/mL vs 217.97 AU/mL, p = 0.003 and 60% vs 93.8%, p = 0.021, respectively). Ruxolitinib, which was the ongoing treatment in five patients with myelofibrosis and three with polycythemia vera, may be implicated in reducing vaccine immunogenicity (p = 0.076), though large prospective study is needed to address this issue.
Disease burden and quality of life in children with sickle cell disease in Italy: time to be considered a priority
Authors: Colombatti Raffaella , Casale Maddalena , Russo Giovanna
Published: July 2021

The objective of the present article is to highlight the need for attention to Quality of Life of patients with Sickle Cell Disease living in Italy. The transformation of sickle cell disease from a severe life-threatening disease of childhood into a chronic, lifelong condition due to the significant improvements in care and treatment options, imposes increasing new challenges to health care providers and patients. Patients now face physical, psychosocial and emotional challenges throughout their lives. They generally have to receive chronic treatments and regular multidisciplinary monitoring which increase social and emotional burden rendering adherence to treatment sometimes complicated. A chronic disease impacts all aspects of patients’ lives, not only the physical one, but also the social and emotional aspects as well as the educational and working life. The entire “Quality of Life” is affected and recent evidence demonstrates the importance quality of life has for patients with chronic illness. The results of this review focus on emerging data regarding quality of life across the lifespan of patients with Sickle Cell Disease, and highlight the need for more action in this field in Italy, where recent immigration and improved care determine an increasing population of children with sickle cell disease being taken into long term care.
Association between the use of balanced fluids and outcomes in critically ill children: a before and after study
Authors: Barhight Matthew F. , Nelson Delphine , Moran Thomas , Christiano Jessica , Sanchez-Pinto L. Nelson
Published: July 2021

Background

Hyperchloremia and chloride load have been associated with worse clinical outcomes in critically ill patients. We sought to evaluate the electrolyte profile and clinical outcomes associated with a unit-wide transition from saline to balanced fluids for resuscitation and maintenance fluids in a pediatric intensive care unit (PICU).

Methods

A before and after analysis of all patients admitted to the PICU in a large, urban, academic hospital between August 2018 and March 2020. The transition from the use of saline to the use of balanced fluids for both resuscitation and maintenance fluid as standard care occurred in June 2019. The primary outcome was day 3 acute kidney injury (AKI). The secondary outcomes included mortality, ventilator-free days (VFDs), need for renal replacement therapy (RRT), hospital length of stay (LOS), and electrolyte abnormalities.

Results

Overall, 2863 patients (47% female) with a day 3 AKI rate of 12.9% (n = 130) and a mortality rate of 2.8% (n = 79) were included. After adjusting for confounders (age, PRISM III, mechanical ventilation, and immunocompromised state, septic shock), there were no significant differences in the odds of day 3 AKI (pre 13%, post 12.5%; adjusted odds ratio [aOR] 0.96, 95%CI 0.65–1.42). There were no differences in the secondary outcomes. The post-intervention period had fewer patients with hyperchloremia (pre 15.5% vs. post 10.4%,p =  < 0.0001) and hyperkalemia (pre 3.2% vs. post 1.4%,p = 0.02) and more patients with hypochloremia (pre 9.5% vs. post 14.4%,p =  < 0.0001) and hypokalemia (pre 38.2% vs. post 47.2%,p =  < 0.0001). In reference to the normochloremic cohort, the hypochloremic cohort had an increase in day 3 AKI, need for RRT, hyperchloremia, and hyperkalemia, and a decrease in hypokalemia; and the hyperchloremic cohort had an increase in VFD and a decrease in hospital LOS.

Conclusions

Following a unit-wide implementation of balanced fluids as standard care, there were no differences in rates of day 3 AKI or other clinical outcomes. However, there were lower rates of hyperkalemia and hyperchloremia and higher rates of hypokalemia and hypochloremia. Further evaluation of the effect of balanced fluids and the clinical significance of electrolyte abnormalities in critically ill children is needed.
Genome wide DNA methylation analysis of alveolar capillary dysplasia lung tissue reveals aberrant methylation of genes involved in development including the FOXF1 locus
Authors: Slot Evelien , Boers Ruben , Boers Joachim , van IJcken Wilfred F. J. , Tibboel Dick , Gribnau Joost , Rottier Robbert , de Klein Annelies
Published: July 2021

Background

Alveolar capillary dysplasia with or without misalignment of the pulmonary veins (ACD/MPV) is a lethal congenital lung disorder associated with a variety of heterozygous genomic alterations in the FOXF1 gene or its 60 kb enhancer. Cases without a genomic alteration in the FOXF1 locus have been described as well. The mechanisms responsible for FOXF1 haploinsufficiency and the cause of ACD/MPV in patients without a genomic FOXF1 variant are poorly understood, complicating the search for potential therapeutic targets for ACD/MPV. To investigate the contribution of aberrant DNA methylation, genome wide methylation patterns of ACD/MPV lung tissues were compared with methylation patterns of control lung tissues using the recently developed technique Methylated DNA sequencing (MeD-seq).

Results

Eight ACD/MPV lung tissue samples and three control samples were sequenced and their mutual comparison resulted in identification of 319 differentially methylated regions (DMRs) genome wide, involving 115 protein coding genes. The potentially upregulated genes were significantly enriched in developmental signalling pathways, whereas potentially downregulated genes were mainly enriched in O-linked glycosylation. In patients with a large maternal deletion encompassing the 60 kb FOXF1 enhancer, DNA methylation patterns in this FOXF1 enhancer were not significantly different compared to controls. However, two hypermethylated regions were detected in the 60 kb FOXF1 enhancer of patients harbouring a FOXF1 point mutation. Lastly, a large hypermethylated region overlapping the first FOXF1 exon was found in one of the ACD/MPV patients without a known pathogenic FOXF1 variation.

Conclusion

This is the first study providing genome wide methylation data on lung tissue of ACD/MPV patients. DNA methylation analyses in the FOXF1 locus excludes maternal imprinting of the 60 kb FOXF1 enhancer. Hypermethylation at the 60 kb FOXF1 enhancer might contribute to FOXF1 haploinsufficiency caused by heterozygous mutations in the FOXF1 coding region. Interestingly, DNA methylation analyses of patients without a genomic FOXF1 variant suggest that abnormal hypermethylation of exon 1 might play a role in some ACD/MPV in patients.
Interplay of Val66Met and BDNF methylation: effect on reward learning and cognitive performance in major depression
Authors: Bakusic J. , Vrieze E. , Ghosh M. , Pizzagalli D. A. , Bekaert B. , Claes S. , Godderis L.
Published: July 2021

Background

There is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD.

Methods

We recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing.

Results

BDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD.

Conclusions

Our results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.
Multifarious functional traits of free-living rhizospheric fungi, with special reference to Aspergillus spp. isolated from North Indian soil, and their inoculation effect on plant growth
Authors: Imran Mohd , Abulreesh Hussein H. , Monjed Mohammad K. , Elbanna Khaled , Samreen  , Ahmad Iqbal
Published: July 2021

Purpose

Rhizospheric soil fungi are critical for plant and soil health. However, their multiple functional traits and impact on plant growth have not been systematically explored.

Methods

During this study, biochemical traits of 73 indigenous soil fungal isolates and 15 unidentified isolates related to plant growth promotion and production of extracellular enzymes were studied.

Results

Forty four (65.67%) of the total isolates produced indole acetic acid (IAA) followed by siderophore (52.23%), phosphate solubilization (37.31%), and antibiotic (11.93%). 91.04% of the studied isolates produced ammonia whereas 28.35% produced organic acid. Extracellular enzyme activities of lipase, amylase, chitinase, and cellulase were detected among 95.52%, 61.11%, 35.82%, and 41.79% isolates, respectively. Based on these activities, 73 fungal isolates were categorized into different biotypes. Quantitative analysis of IAA production and phosphate solubilization was carried out for Aspergillus, Penicillium, and Rhizopus isolates. Aspergillus isolates exhibited varying activities of IAA production and phosphate solubilization. Most of the Aspergillus isolates and some other fungi demonstrated multiple activities. Based on the multiple traits of selected fungal isolates, Aspergillus sp-07, Penicillium sp-03, and Rhizopus sp-02 were further evaluated in different combinations for their inoculation effect on the growth and yield of wheat under field conditions.

Conclusions

The results indicated that these isolates could be developed into bio-inoculants to enhance plant growth. The consortium of these three isolates was also found to be compatible and beneficial for plant growth.
Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic
Authors: Rousseau Anne-Françoise , Minguet Pauline , Colson Camille , Kellens Isabelle , Chaabane Sourour , Delanaye Pierre , Cavalier Etienne , Chase J. Geoffrey , Lambermont Bernard , Misset Benoit
Published: July 2021

Purpose

Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3).

Patients and methods

All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine.

Results

Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49–68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61–80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8–17.7] mg/L).

Conclusion

The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.
Nonlinear differential equations with perturbed Dirichlet integral boundary conditions
Authors: Cabada Alberto , Iglesias Javier
Published: July 2021

This paper is devoted to prove the existence of positive solutions of a second order differential equation with a nonhomogeneous Dirichlet conditions given by a parameter dependence integral. The studied problem is a nonlocal perturbation of the Dirichlet conditions by considering a homogeneous Dirichlet-type condition at one extreme of the interval and an integral operator on the other one. We obtain the expression of the Green’s function related to the linear part of the equation and characterize its constant sign. Such a property will be fundamental to deduce the existence of solutions of the nonlinear problem. The results hold from fixed point theory applied to related operators defined on suitable cones.
Some properties of implicit impulsive coupled system via φ-Hilfer fractional operator
Authors: Almalahi Mohammed A. , Panchal Satish K.
Published: July 2021

The major goal of this work is investigating sufficient conditions for the existence and uniqueness of solutions for implicit impulsive coupled system ofφ-Hilfer fractional differential equations (FDEs) with instantaneous impulses and terminal conditions. First, we derive equivalent fractional integral equations of the proposed system. Next, by employing some standard fixed point theorems such as Leray–Schauder alternative and Banach, we obtain the existence and uniqueness of solutions. Further, by mathematical analysis technique we investigate the Ulam–Hyers (UH) and generalized UH (GUH) stability of solutions. Finally, we provide a pertinent example to corroborate the results obtained.
System of fractional boundary value problem with p-Laplacian and advanced arguments
Authors: Mahdjouba Amina , Nieto Juan J. , Ouahab Abdelghani
Published: July 2021

In this paper, we discuss the existence and multiplicity of positive solutions for a system of fractional differential equations with boundary condition and advanced arguments. The existence result is proved via Leray–Schauder’s fixed point theorem type in a vector Banach space. Further, by using a new fixed point theorem in order Banach space, we study the multiplicity of positive solutions. Finally, some examples are given to illustrate our results.
Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial
Authors: Pan Jing , Tan Yue , Wang Guoling , Deng Biping , Ling Zhuojun , Song Weiliang , Seery Samuel , Zhang Yanlei , Peng Shuixiu , Xu Jinlong , Duan Jiajia , Wang Zelin , Yu Xinjian , Zheng Qinlong , Xu Xiuwen , Yuan Ying , Yan Fangrong , Tian Zhenglong , Tang Kaiting , Zhang Jiecheng , Chang Alex H. , Feng Xiaoming
Published: July 2021

PURPOSE

Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL.

METHODS

In this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 × 105or 1 × 106(±30%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary.

RESULTS

Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n = 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency.

CONCLUSION

Among 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress ( NCT04689659 ).
An Integrated Analysis of Dostarlimab Immunogenicity
Authors: Lu Sharon , Bowsher Ronald R. , Clancy Amanda , Rosen Amy , Zhang Mingxuan , Yang Ying , Koeck Kathleen , Gao Minggeng , Potocka Elizabeth , Guo Wei , Jen Kai Yu , Im Ellie , Milton Ashley
Published: July 2021

Monoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may represent a significant challenge to both efficacy and safety in some patients. Dostarlimab (TSR-042) is an approved, humanized, anti-PD-1 monoclonal antibody that has shown efficacy in multiple solid tumor types. Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study. Overall, 477 of 478 patients (99.8%) were included in the analysis of dostarlimab antibody prevalence, and 349 out of 478 enrolled patients (73.0%) were evaluable for treatment-emergent antibodies to dostarlimab. The incidence of treatment-emergent ADAs was 2.5% at the recommended therapeutic dose (500 mg Q3W for the first 4 doses, 1000 mg Q6W until discontinuation), which is comparable to other anti-PD-(L)1 drugs. NAbs were detected in only 1.3% of patients. In the small percentage of patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab at the recommended dosing regimen. These findings demonstrated that treatment with dostarlimab was associated with a low risk of eliciting clinically meaningful ADAs over the course of this study, and dostarlimab is already approved by health authorities.
Washington Consensus Reforms and Lessons for Economic Performance in Sub-Saharan Africa
Authors: Archibong Belinda , Coulibaly Brahima , Okonjo-Iweala Ngozi
Published: July 2021

Over three decades after market-oriented structural reforms termed “Washington Consensus” policies were first implemented, we revisit the evidence on policy adoption and the effects of these policies on socio-economic performance in sub-Saharan African countries. We focus on three key ubiquitous reform policies around privatization, fiscal discipline, and trade openness and document significant improvements in economic performance for reformers over the past two decades. Following initial declines in per capita economic growth over the 1980s and 1990s, reform adopters experienced notable increases in per capita real GDP growth in the post-2000 period. We complement aggregate analysis with four country case studies that highlight important lessons for effective reform. Notably, the ability to implement pro-poor policies alongside market-oriented reforms played a central role in successful policy performance.
Statistical Significance,p-Values, and the Reporting of Uncertainty
Authors: Imbens Guido W.
Published: July 2021

The use of statistical significance and p-values has become a matter of substantial controversy in various fields using statistical methods. This has gone as far as some journals banning the use of indicators for statistical significance, or even any reports of p-values, and, in one case, any mention of confidence intervals. I discuss three of the issues that have led to these often-heated debates. First, I argue that in many cases, p-values and indicators of statistical significance do not answer the questions of primary interest. Such questions typically involve making (recommendations on) decisions under uncertainty. In that case, point estimates and measures of uncertainty in the form of confidence intervals or even better, Bayesian intervals, are often more informative summary statistics. In fact, in that case, the presence or absence of statistical significance is essentially irrelevant, and including them in the discussion may confuse the matter at hand. Second, I argue that there are also cases where testing null hypotheses is a natural goal and where p-values are reasonable and appropriate summary statistics. I conclude that banning them in general is counterproductive. Third, I discuss that the overemphasis in empirical work on statistical significance has led to abuse of p-values in the form of p-hacking and publication bias. The use of pre-analysis plans and replication studies, in combination with lowering the emphasis on statistical significance may help address these problems.
Why Is Growth in Developing Countries So Hard to Measure?
Authors: Angrist Noam , Goldberg Pinelopi Koujianou , Jolliffe Dean
Published: July 2021

Occasional widely publicized controversies have led to the perception that growth statistics from developing countries are not to be trusted. Based on the comparison of several data sources and analysis of novel IMF audit data, we find no support for the view that growth is on average measured less accurately or manipulated more in developing than in developed countries. While developing countries face many challenges in measuring growth, so do higher-income countries, especially those with complex and sometimes rapidly changing economic structures. However, we find consistently higher dispersion of growth estimates from developing countries, lending support to the view that classical measurement error is more problematic in poorer countries and that a few outliers may have had a disproportionate effect on (mis)measurement perceptions. We identify several measurement challenges that are specific to poorer countries, namely limited statistical capacity, the use of outdated data and methods, the large share of the agricultural sector, the informal economy, and limited price data. We show that growth measurement based on the System of National Accounts (SNA) can be improved if supplemented with information from other data sources (for example, satellite-based data on vegetation yields) that address some of the limitations of SNA.
Retrospectives: James Buchanan: Clubs and Alternative Welfare Economics
Authors: Marciano Alain
Published: July 2021

James Buchanan wrote “An Economic Theory of Clubs” and invented clubs to support a form of welfare economics in which there is no social welfare function (SWF) and individual utility functions cannot be “read” by external observers. Clubs were a means to allow the implementation of individualized prices for public goods and services and to allow each individual to pay exactly the amount he wants to pay. He developed this project to answer and counter Paul Samuelson's analysis of public goods, in which social welfare functions play a crucial role. Buchanan and Samuelson disagreed over the allocation of the costs of the public good to each individual. To Buchanan, it was by relying on individual's preferences. To Samuelson, by using a SWF. Buchanan's clubs are thus foreign and incompatible with the traditional Samuelson-style public economics in which they are used.
The challenge of applying digital image processing software on intraoral radiographs for osteoporosis risk assessment
Authors: Gullberg Joanna , Al-Okshi Ayman , Homar Asan Dalia , Zainea Anita , Sundh Daniel , Lorentzon Mattias , Lindh Christina
Published: July 2021

Objectives:

The purpose of this study was to evaluate rater agreement and the accuracy of a semi-automated software and its fully automated tool for osteoporosis risk assessment in intraoral radiographs.

Methods:

A total of 567 intraoral radiographs was selected retrospectively from women aged 75–80 years participating in a large population-based study (SUPERB) based in Gothenburg, Sweden. Five raters assessed participants’ risk of osteoporosis in the intraoral radiographs using a semi-automated software. Assessments were repeated after 4 weeks on 121 radiographs (20%) randomly selected from the original 567. Radiographs were also assessed by the softwares’ fully automated tool for analysis.

Results:

Overall interrater agreement for the five raters was 0.37 (95% CI 0.32–0.41), and for the five raters with the fully automated tool included as ‘sixth rater’ the overall Kappa was 0.34 (0.30–0.38). Intrarater agreement varied from moderate to substantial according to the Landis and Koch interpretation scale. Diagnostic accuracy was calculated in relation to reference standard for osteoporosis diagnosis which is T-score values for spine, total hip and femoral neck and presented in form of sensitivities, specificities, predictive values, likelihood ratios and odds ratios. All raters' mean sensitivity, including the fully automated tool, was 40,4% (range 14,3%–57,6%). Corresponding values for specificity was 69,5% (range 59,7%–90,4%). The diagnostic odds ratios ranged between 1 and 2.7.

Conclusion:

The low diagnostic odds ratio and agreement between raters in osteoporosis risk assessment using the software for analysis of the trabecular pattern in intraoral radiographs shows that more work needs to be done to optimise the automation of trabecular pattern analysis in intraoral radiographs.
Responsible Citizens against an Irresponsible State: The Case of Greece amidst the COVID-19 Pandemic
Authors: Alexopoulou Sofia , Pavli Antonia
Published: July 2021

How is it possible for citizens to act responsibly if they live in an irresponsible state? This is the key question that this paper revolves around in the context of the COVID-19 pandemic in Greece. Individual responsibility is the dominant ‘mantra’ of post-modernity and is widely spread by the neoliberal dogma. The individual has to take care of him/herself in any possible way to avoid risks without depending so much on the benevolent state, which, in the developed world, takes the form of a welfare state. Thus, a new type of citizen appears, the “responsible citizen”. The oxymoron, however, in the Greek case is that the state and particularly the political elites maintain bad practices of the past without being able to overcome the country’s path-dependency structures by acting responsibly. The concept of “empathy” is undoubtedly the missing link in this intriguing puzzle of good governance. Will the Greek political elites be able to recognize and embrace empathy in practice?
Self-Defense Mechanisms of Democracy during the Crisis: The Baltic States in Comparative Perspective
Authors: Rak Joanna
Published: July 2021

Theoretically embedded in studies on militant democracy, the study offers a comparative analysis of the use of self-defense mechanisms of democracy during the Coronavirus Crisis in Estonia, Lithuania, and Latvia. The research aims to identify what anti-democratic measures were adopted to influence the sovereignty of the political nations and which served to either strengthen, maintain or undermine that sovereignty. Although neo-militant democracy goals prevailed in the Baltic states’ pre-pandemic political and legal structures, the pandemic-induced measures resulted in variation. In Estonia, the restrictions put the sovereignty of the political nation in jeopardy. Simultaneously, in Lithuania and Latvia, the sovereignty of the political nations remained unthreatened. In Estonia, the electoral successes and increase in support for the extreme-right political party Conservative People’s Party of Estonia turned conducive to the movement from neo- towards quasi-militant democracy. In Lithuania and Latvia, the extreme groupings did not receive comparable support and could not initiate an anti-democratic turn.
Digital Arenas: The regulatory framework and other relevant issues on eSports online betting
Authors: Sykas Stylianos
Published: July 2021

The contribution of technological development, in an essential and user-friendly way, to the transition of many aspects of the real world to the digital environment, is constantly creating new habits and new fields of activity. This transition, without any shadow of doubt, leads to new and unknown realities, which, apart from the interest they present, they call for thorough investigation and further regulation, where it is needed. The cases of eSports and online gaming, although not new to the user of the digital age, are of high importance to the investment and commercial world, in terms of their further development and exploitation. In this context, although online betting in eSports has been introduced to the Greek market a few years ago, it is unlikely to be developed according to its dynamics, since issues of legal nature are not settled yet. In order to ensure a secure landscape for eSports online betting, the necessity for transparency and integrity and their protection through regulatory action becomes imperative.
Case Report: A giant fecaloma revealed by severe aspiration pneumonia and urinary retention
Authors: Mchirgui Elhem , Elloumi Hanen , Ganzoui Imen , Triki Wissem
Published: July 2021

Fecaloma is an accumulation of hardened impacted stool typically occurring in the sigmoid colon and rectum. It mainly affects elderly and bedridden patients suffering from chronic constipation and can be revealed by different signs. We report a case of 74-year-old female, with anorexia, Alzheimer’s disease, and chronic constipation, who was admitted to the emergency department with complaints of dyspnea and anuria. Clinical examination showed fever, Glasgow Coma Scale score of 13/15, tachycardia with a blood pressure of 100/50 mmHg, polypnea with hypoxia, foci of crepitant rales in pulmonary auscultation and a tender hypogastric mass with mild diffuse abdominal tenderness. Digital rectal examination revealed hard fecal material. Computed tomography (CT) images demonstrated bilateral pulmonary parenchymal condensation and a huge heterogeneous fecaloma in the sigmoid colon and rectum compressing the bladder. Based on these findings, the diagnosis of giant fecaloma causing aspiration pneumonia and urinary retention was retained. Manual disimpaction and bowel enemas were done but they were unsuccessful and surgical treatment was refused. Ultimately the patient died due to septic shock. Early diagnosis should be made to relieve symptoms and prevent complications.