bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Functional Annotation of Metagenomes and Microbial Genomes Using a Deep Learning-Based Method
Authors: Maranga Mary , Szczerbiak Pawel , Bezshapkin Valentyn , Gligorijevic Vladimir , Chandler Chris , Bonneau Richard , Xavier Ramnik J. , Vatanen Tommi , Kosciolek Tomasz
Published: April 2023

The past decade has seen advancement in high-throughput sequencing technologies resulting in rapid accumulation of genomic data from microbial communities. While this growth in sequence data and gene discovery is impressive, the majority of microbial gene functions remain uncharacterized.
Combined unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction in a young patient with post-traumatic arthritis
Authors: Madan Fatema , Alsooreti Ahmed , Guatteri Gianluca Cusma
Published: April 2023

Post-traumatic arthritis can result in significant pain and difficulty in managing daily life activities. Multiple factors are weighed in selecting the proper surgical intervention, with patient age and level of activity being most important. Isolated osteoarthritis is a well-known indication for unicompartmental knee arthroplasty, where a better range of motion, preservation of natural knee kinematics and less invasive resection of knee joint bone are used. Moreover, the high improvement rate and long-term results after anterior cruciate ligament (ACL) reconstruction and restoration of knee stability can make the combined procedure favourable, particularly for young active patients.

We report on an active man in his 30s presenting with isolated medial compartment advanced arthritis after sustaining distal femur intra-articular fracture. He was initially treated with partial unicompartmental knee replacement combined with ACL reconstruction, delivering a good short-term follow-up outcome.

Though this case involves just a single patient, the positive outcome suggests that combined partial unicompartmental knee replacement with an ACL reconstruction should be considered for young and active patients diagnosed with isolated advanced medial compartment osteoarthritis.
Tele-UPCAT: study protocol of a randomised controlled trial of a home-based Tele-monitored UPper limb Children Action observation Training for participants with unilateral cerebral palsy
Authors: Sgandurra Giuseppina , Cecchi Francesca , Beani Elena , Mannari Irene , Maselli Martina , Falotico Francesco Paolo , Inguaggiato Emanuela , Perazza Silvia , Sicola Elisa , Feys Hilde , Klingels Katrijn , Ferrari Adriano , Dario Paolo , Boyd Roslyn N , Cioni Giovanni
Published: April 2023

Introduction

A new rehabilitative approach, called UPper Limb Children Action Observation Training (UPCAT), based on the principles of action observation training (AOT), has provided promising results for upper limb rehabilitation in children with unilateral cerebral palsy (UCP). This study will investigate if a new information and communication technology platform, named Tele-UPCAT, is able to deliver AOT in a home setting and will test its efficacy on children and young people with UCP.

Methods and analysis

A randomised, allocation concealed (waitlist control) and evaluator-blinded clinical trial with two investigative arms will be carried out. The experimental group will perform AOT at home for 3 weeks using a customised Tele-UPCAT system where they will watch video sequences of goal-directed actions and then complete the motor training of the same actions. The control group will receive usual care for 3 weeks, which may include upper limb training. They will be offered AOT at home after 3 weeks. Twenty-four children with UCP will be recruited for 12 participants per group. The primary outcome will be measured using Assisting Hand Assessment. The Melbourne Assessment 2, ABILHAND, Participation and Environment Measure-Children and Youth and Cerebral Palsy Quality of Life Questionnaire will be included as secondary measures. Quantitative measures from sensorised objects and participants worn Actigraphs GXT3+ will be analysed. The assessment points will be the week before (T0) and after (T1) the period of AOT/standard care. Further assessments will be at T1 plus, the week after the AOT period for the waitlist group and at 8 weeks (T2) and 24 weeks (T3) after AOT training.

Ethics and dissemination

The trial has been approved by the Tuscany Paediatric Ethics Committee (169/2016). Publication of all outcomes will be in peer-reviewed journals and conference presentations.

Trial registration

NCT03094455.
Aetiology of ear infection and antimicrobial susceptibility pattern among patients attending otorhinolaryngology clinic at a tertiary hospital in Dar es Salaam, Tanzania: a hospital-based cross-sectional study
Authors: Shangali Aminiel , Kamori Doreen , Massawe Willybroad , Masoud Salim , Kibwana Upendo , Mwingwa Anthony G , Manisha Anselmo , Mwandigha Ambele M , Mirambo Mariam M , Mshana Stephen E , Manyahi Joel , Majigo Mtebe
Published: April 2023

Objectives

To determine the aetiological pathogens causing ear infections and their antimicrobial susceptibility patterns among patients with ear complaints at a tertiary hospital in Dar es Salaam.

Design

Hospital-based cross-sectional study.

Settings

Otorhinolaryngology clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania.

Participants

Patients presenting with signs and symptoms of ear infection.

Main outcome measure

Bacteria and fungi isolated from ear swab specimens of patients presenting with signs and symptoms of ear infection; and antimicrobial susceptibility patterns of isolated bacteria.

Results

Two hundred and fifty-five participants were enrolled, with a median age of 31 years and an IQR of 15–49. Otitis externa was the predominant type of ear infection, accounting for 45.1%. We observed positive bacteria culture in 53.3% of study participants, in which 41% of isolates were obtained from patients with chronic suppurative otitis media. Moreover,Staphylococcus aureus(27.3%) andPseudomonas aeruginosa(24.2%) were the most frequently isolated bacteria, whileCandidaspp, 12 (63.8%) andAspergillusspp, 9 (36.2%) were the only isolated fungi. Furthermore, we report that 93% of isolatedEnterobacteraleswere resistant to amoxicillin/clavulanic acid, and 73% were resistant to ceftazidime. In addition, we detected 34.4% extended-spectrum beta-lactamase-producingEnterobacterales(ESBL-PE) and 44.4% methicillin-resistanceS. aureus(MRSA). We also found that 22% of the bacteria isolates were resistant to ciprofloxacin, a primary topical antibiotic used in managing ear infections.

Conclusions

The findings from this study reveal that the leading aetiological agent of ear infection is bacteria. Furthermore, our findings show a significant proportion of ESBL-PE and MRSA-causing ear infections. Hence, detecting multidrug-resistant bacteria is crucial to improving ear infection management.
Evaluating safety and effectiveness of the early-onset sepsis calculator to reduce antibiotic exposure in Dutch at-risk newborns: a protocol for a cluster randomised controlled trial
Authors: van der Weijden Bo M , van der Weide Marijke C , Plötz Frans B , Achten Niek B
Published: April 2023

Introduction

Newborns are at risk for early-onset sepsis (EOS). In the Netherlands, EOS affects less than 0.2% of newborns, but approximately 5% are treated with empirical antibiotics. These numbers form an example of overtreatment in countries using risk-factor based guidelines for administrating antibiotics. An alternative to these guidelines is the EOS calculator, a tool that calculates an individual EOS risk and provides management recommendation. However, validation outside the North-American setting is limited, especially for safety outcomes. We aim to investigate whether EOS calculator use can safely reduce antibiotic exposure in newborns with suspected EOS compared with the Dutch guideline.

Methods and analysis

This protocol describes a cluster randomised controlled trial assessing whether EOS calculator use is non-inferior regarding safety, and superior regarding limiting overtreatment, compared with the Dutch guideline. We will include newborns born at ≥34 weeks’ gestation, with at least one risk factor consistent with EOS within 24 hours after birth. After 1:1 randomisation, the 10 participating Dutch hospitals will use either the Dutch guideline or the EOS calculator as standard of care for all newborns at risk for EOS. In total, 1830 newborns will be recruited. The coprimary non-inferiority outcome will be the presence of at least one of four predefined safety criteria. The coprimary superiority outcome will be the proportion of participants starting antibiotic therapy for suspected and, or proven EOS within 24 hours after birth. Secondary outcomes will be the total duration of antibiotic therapy, the percentage of antibiotic therapy started between 24 and 72 hours after birth, and parent-reported quality of life. Analyses will be performed both as intention to treat and per protocol.

Ethics and dissemination

This trial has been approved by the Medical Ethics Committee of the Amsterdam UMC (NL78203.018.21). Results will be presented in peer-reviewed journals and at international conferences.

Trial registration number

NCT05274776.
Barriers and facilitators of deceased organ donation among Muslims living globally: protocol for an integrative systematic review using narrative synthesis
Authors: Al-Abdulghani Asmaa , Vincent Britzer Paul , Randhawa Gurch , Cook Erica , Fadhil Riadh
Published: April 2023

Introduction

Muslims have been shown to have less favourable attitudes towards organ donation and are less likely to consent to donate their organs. While several studies have been undertaken globally to identify the barriers and facilitators of organ donation, no systematic review has synthesised this evidence to date. Therefore, this systematic review aims to identify the barriers and facilitators of organ donation among Muslims living globally.

Methods and analysis

This systematic review will include cross-sectional surveys and qualitative studies published between 30 April 2008 and 30 June 2023. Evidence will be restricted only to studies reported in English. An extensive search strategy will be used in PubMed, CINAHL, Medline, Scopus, PsycINFO, Global Health and Web of Science, as well as specific relevant journals that may not be indexed in these databases. A quality appraisal will be undertaken using Joanna Briggs Institute quality appraisal tool. An integrative narrative synthesis will be used to synthesise the evidence.

Ethics and dissemination

Ethical approval has been obtained from the Institute for Health Research Ethics Committee (IHREC) (IHREC987), University of Bedfordshire. The findings of this review will be disseminated widely through peer-reviewed journal articles and leading international conferences.

PROSPERO registration number

CRD42022345100.
Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression
Authors: Drake Wonder P , Hsia Connie , Samavati Lobelia , Yu Michelle , Cardenas Jessica , Gianella Fabiola G , Boscardin John , Koth Laura L
Published: April 2023

Introduction

Sarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk stratification tools for important clinical outcomes in sarcoidosis, such as progressive lung disease. This study will address two clinical practice needs: (1) development of a risk calculator that provides an estimate of the likelihood of pulmonary progression in sarcoidosis patients during the follow-up period and (2) determine the optimal interval for serial clinical monitoring (eg, 6, 12, 18 months) using these risk prediction tools.

Methods and analysis

The Risk Indicators of Sarcoidosis Evolution-Unified Protocol study is a National Institutes of Health-sponsored, longitudinal observational study of adults with pulmonary sarcoidosis who will be enrolled at five US tertiary care centres. Participants will be evaluated at approximately 6-month intervals for up to 60 months with collection of lung function, blood samples and clinical data. The target sample size is 557 and the primary objective is to determine which clinical features measured during a routine clinic visit carry the most prognostic information for predicting clinical progression of pulmonary sarcoidosis over the follow-up period. The primary outcome measure will be quantified by a clinically meaningful change in forced vital capacity, forced expiratory volume in 1 s or diffusing capacity of the lung for carbon monoxide. The secondary objective is to determine if blood biomarkers measured during a routine clinic visit can improve the risk assessment modelling for progression of pulmonary sarcoidosis over the follow-up period.

Ethics and dissemination

The study protocol has been approved by the Institutional Review Boards at each centre and the reliance Institutional Review Board overseeing the study (WCG, Protocol #20222400). Participants will provide informed consent prior to enrolment. Results will be disseminated via publication in a relevant peer-reviewed journal.

Trial registration number

NCT05567133.
$$\Lambda _b \rightarrow p, N^*(1535)$$ form factors from QCD light-cone sum rules
Authors: Huang Ke-Sheng , Liu Wei , Shen Yue-Long , Yu Fu-Sheng
Published: April 2023

In this work, we calculate the transition form factors of $$\Lambda _b$$

Λ
b

decaying into proton and $$N^*(1535)$$

N
∗

(
1535
)

($$J^P={1/2}^+$$

J
P

=

1
/
2

+

and $${1/2}^-$$

1
/
2

-

respectively) within the framework of light-cone sum rules with the distribution amplitudes (DAs) of $$\Lambda _b$$

Λ
b

-baryon. In the hadronic representation of the correlation function, we have isolated both the proton and the $$N^*(1535)$$

N
∗

(
1535
)

states so that the $$\Lambda _b \rightarrow p, N^*(1535)$$

Λ
b

→
p
,

N
∗

(
1535
)

form factors can be evaluated simultaneously. Due to the less known properties of the baryons, we investigate three interpolating currents of the light baryons and five parametrization models for DAs of $$\Lambda _b $$

Λ
b

. Numerically, our predictions on the $$\Lambda _b \rightarrow p$$

Λ
b

→
p

form factors and the branching fractions of $$\Lambda _b\rightarrow p\ell \nu $$

Λ
b

→
p
ℓ
ν

from the Ioffe or the tensor currents are consistent with the Lattice simulation and the results from the light-baryon sum rules, as well as the experimental data of $$Br(\Lambda _b^0\rightarrow p\mu ^-{{\bar{\nu }}})$$

B
r
(

Λ
b
0

→
p

μ
-

ν

¯

)

. The predictions on the form factors of $$\Lambda _b \rightarrow N^*(1535)$$

Λ
b

→

N
∗

(
1535
)

are very sensitive to the choice of the interpolating currents so that the relevant measurement could be helpful to clarify the properties of baryons.
Top quark mass measurements at the $$t\bar{t}$$ threshold with CEPC
Authors: Li Zhan , Sun Xiaohu , Fang Yaquan , Li Gang , Xin Shuiting , Wang Shudong , Wang Yiwei , Zhang Yuan , Zhang Hao , Liang Zhijun
Published: April 2023

We present a study of top quark mass measurements at the $$t\bar{t}$$

t

t

¯

threshold based on CEPC. A centre-of-mass energy scan near two times of the top quark mass is performed and the measurement precision of top quark mass, width and $$\alpha _S$$

α
S

are evaluated using the $$t\bar{t}$$

t

t

¯

production rates. Realistic scan strategies at the threshold are discussed to maximise the sensitivity to the measurements individually and simultaneously in the CEPC scenarios assuming a total luminosity limited to 100 fb$$^{-1}$$

-
1

. With the optimal scan for individual property measurements, the top quark mass precision is expected to be 9 MeV, the top quark width precision is expected to be 26 MeV, and $$\alpha _S$$

α
S

can be measured at a precision of 0.00039, considering only the statistical uncertainty. Taking into account the systematic uncertainties from theory, width, $$\alpha _S$$

α
S

, experimental efficiency, background subtraction, beam energy and luminosity spectrum, the top quark mass can be measured at a precision of 25 MeV optimistically and 59 MeV conservatively at CEPC.
Changing Trade Pattern, ICT, and Employment: Evidence Across Countries
Authors: Sharma Manish Kumar , Aditya Anwesha
Published: April 2023

This paper examines the impact of export diversification and ICT on aggregate and skill-level employment for a sample of 45 and 33 countries from 1990 to 2019 and 1995 to 2019 for OECD & G20 country groups. GMM dynamic panel estimation results suggest that more product-wise concentrated exports lead to new employment opportunities overall, but not geographically diversified exports. Internet has substitution effects on overall employment whereas mobile is insignificant. A greater product-wise diversified export structure expands low-skill-intensive jobs, but greater geographical diversification expands high-skill-intensive jobs. Internet use promotes high-skill-intensive jobs but displaces low-skilled workers. Mobile is found to expand job opportunities for low-skilled workers.
Community Health Worker Integration with and Effectiveness in Health Care and Public Health in the United States
Authors: Knowles Molly , Crowley Aidan P. , Vasan Aditi , Kangovi Shreya
Published: April 2023

Community health workers (CHWs) have worked in a variety of settings in the United States for more than 70 years and are increasingly recognized as an essential health workforce. CHWs share life experience with the people they serve and have firsthand knowledge of the causes and impacts of health inequity. They provide a critical link between marginalized communities and health care and public health services. Several studies have demonstrated that CHWs can improve the management of chronic conditions, increase access to preventive care, improve patients’ experience of care, and reduce health care costs. CHWs can also advance health equity by addressing social needs and advocating for systems and policy change. This review provides a history of CHW integration with health care in the United States; describes evidence of the impact of CHW programs on population health, experience, costs of care, and health equity; and identifies considerations for CHW program expansion.
eEF1A2 siRNA Suppresses MPP+-Induced Activation of Akt and mTOR and Potentiates Caspase-3 Activation in a Parkinson’s Disease Model
Authors: Khwanraj Kawinthra , Prommahom Athinan , Dharmasaroja Permphan
Published: April 2023

The tissue-specific protein eEF1A2 has been linked to the development of neurological disorders. The role of eEF1A2 in the pathogenesis of Parkinson’s disease (PD) has yet to be investigated. The aim of this study was to determine the potential neuroprotective effects of eEF1A2 in an MPP+ model of PD. Differentiated SH-SY5Y cells were transfected with eEF1A2 siRNA, followed by MPP+ exposure. The expression of p-Akt1 and p-mTORC1 was determined using Western blotting. The expression of p53, Bax, Bcl-2, and caspase-3 was evaluated using qRT-PCR. Cleaved caspase-3 levels and Annexin V/propidium iodide flow cytometry were used to determine apoptosis. The effects of PI3K inhibition were examined. The results showed that eEF1A2 siRNA significantly reduced the eEF1A2 expression induced by MPP+. MPP+ treatment activated Akt1 and mTORC1; however, eEF1A2 knockdown suppressed this activation. In eEF1A2-knockdown cells, MPP+ treatment increased the expression of p53 and caspase-3 mRNA levels as well as increased apoptotic cell death when compared to MPP+ treatment alone. In cells exposed to MPP+, upstream inhibition of the Akt/mTOR pathway, by either LY294002 or wortmannin, inhibited the phosphorylation of Akt1 and mTORC1. Both PI3K inhibitors increased eEF1A2 expression in cells, whether or not they were also treated with MPP+. In conclusion, eEF1A2 may function as a neuroprotective factor against MPP+, in part by regulating the Akt/mTOR pathway upstream.
[Retracted] Wireless Intelligent Sensor Network in Dynamic Environmental Monitoring of Archaeological Excavation Site
Authors: Ye Nan
Published: April 2023

This paper intends to apply the Intelligent Wireless Sensor Network (IWSN) to the archaeological excavation site and make the dynamic site of archaeological excavation can be monitored intelligently in real‐time. This paper firstly discusses the structure and function of Wireless Sensor Network (WSN). Secondly, according to the problem of limited dynamic monitoring of WSN, an IWSN is established. The dynamic environmental monitoring of archaeological excavation sites is achieved by using Geographic Information System (GIS) and remote sensing technology combined with IWSN. Finally, this paper analyses the environmental monitoring results of the archaeological excavation site, the dynamic environmental monitoring location of the archaeological excavation site of the IWSN, and the simulation results of the Intelligent Wireless Sensor Network‐Geographic Information System (IWSN‐GIS) in the dynamic environmental monitoring of the archaeological excavation site. The results show that the Inverse Distance to a Power (IDP) algorithm in temperature and humidity monitoring data on the overall downward trend, the algorithm performance is relatively stable, and the algorithm performance is better than the other two algorithms. The monitoring performance of IWSN‐GIS system is better than that of IWSN system. It shows that with the increase in the communication distance of sensor nodes, the relative error of different monitoring systems for the dynamic monitoring position of the archaeological excavation site is decreasing. IWSN‐GIS can monitor the environment before, during, and after the archaeological site. This paper realizes the intelligent, scientific, and technological archaeology of archaeological excavation through IWSN, GIS, and remote sensing image technology, and provides technical support for digital archaeology in archaeological research.
[Retracted] Application of Multisource Data Fusion Technology in the Construction of Land Ecological Index
Authors: Hao Juan , Yang Yang , Sun Haoyue , Zhang Zhicheng , Kang Zhanwu , Zhang Jianfang
Published: April 2023

In order to control the grassland ecological environment, an application method of multisource data fusion technology in the construction of land ecological index is proposed. Due to the high requirements for grassland environmental monitoring, the use of traditional technologies to monitor grassland environmental conditions lacks certain effectiveness, has high investment costs, and consumes a lot of manpower and material resources. The use of sensors to dynamically monitor the grassland environment is conducive to monitoring the environment from a scientific and technological level. By understanding the fusion principle and process of three fusion methods, adaptive weighted average, BP neural network, and D‐S evidence theory, the construction of Bashang grassland ecological energy big data platform based on multisource data fusion is proposed. A two‐level data fusion model based on grassland environmental monitoring is proposed. Several environmental parameters in the experimental environment were monitored, and the validity of the two‐level fusion model was verified by two evaluation indicators, the mean absolute percentage error and the corrosion error. This suggests that a combination of BP neural network and D‐S proof theory improves system performance. It provides the possibility for more comprehensive monitoring of grassland ecological environment in the future.
Histological Features of IgA Nephropathy in Pediatrics and the Magnitude of the Disease in Saudi Children
Authors: Al Zahrani Reem A.
Published: April 2023

Objectives. This review addresses the microscopic features of immunoglobulin A nephropathy (IgA nephropathy), its prognostic variables in children, and measures to which extent these features and variables differ from adults. Furthermore, it describes the extent of this disease process among children in Saudi Arabia and the rest of the Arab countries and compares it with the data from the West and the Far East. Method. All the original work described the histological features of pediatric IgA nephropathy, and studies involved in developing the prognostic classification of IgA nephropathy, Oxford Classification, were reviewed. Moreover, the studies describing the crescent prevalence and outcome in pediatric IgA nephropathy in addition to thrombotic microangiopathy association were studied. National studies describing the prevalence of pediatric IgA nephropathy and pediatric crescentic glomerulonephritis were tracked with an overview of the regional data from the rest of the Arab world. Results. IgA nephropathy in children showed more glomerular proliferative changes and less glomerular vascular and tubule-interstitial chronic injury compared to adults. The reference study that described the association between thrombotic microangiopathy and IgA nephropathy did not include the pediatric age group. Moreover, it was found that the data from the Middle East was not encountered in developing the original and updated IgA nephropathy Oxford Classification. Furthermore, the prevalence of IgA nephropathy in children is described in the regional literature, but its histological features were not well detailed. Finally, the percentage of crescentic glomerulonephritis (GN) due to IgA nephropathy is less in our country compared to the West and concords with the Far East findings. Conclusion. A well-designed regional study addressing IgA nephropathy in Middle East children with a focus on histological features, association with crescent, and thrombotic microangiopathy and challenging the validity of the updated IgA nephropathy Oxford Classification is recommended.
Theoretical and Numerical Study for Volterra−Fredholm Fractional Integro-Differential Equations Based on Chebyshev Polynomials of the Third Kind
Authors: Laouar Zineb , Arar Nouria , Ben Makhlouf Abdellatif
Published: April 2023

In this paper, we develop an efficient numerical method to approximate the solution of fractional integro-differential equations (FI-DEs) of mixed Volterra−Fredholm type using spectral collocation method with shifted Chebyshev polynomials of the third kind (S-Cheb-3). The fractional derivative is described in the Caputo sense. A Chebyshev−Gauss quadrature is involved to evaluate integrals for more precision. Two types of equations are studied to obtain algebraic systems solvable using the Gauss elimination method for linear equations and the Newton algorithm for nonlinear ones. In addition, an error analysis is carried out. Six numerical examples are evaluated using different error values (maximum absolute error, root mean square error, and relative error) to compare the approximate and the exact solutions of each example. The experimental rate of convergence is calculated as well. The results validate the numerical approach’s efficiency, applicability, and performance.
Antitubular Basement Membrane Antibody Disease Associated with Nivolumab Infusion and Concomitant Acute Pyelonephritis Leading to Acute Kidney Injury : a Case Report and Literature Review
Authors: Rifai Ahmad Oussama , Denig Kristin M. , Caza Tiffany , Webb Shana M. , Rifai Sarah , Khan Sarah , Dahan Sally , Alamin Samaa
Published: April 2023

Antitubular basement membrane (anti-TBM) antibody disease is an extremely rare disorder. It may be idiopathic or secondary to exposure of the proximal tubular basement membrane, triggered by tubular injury due to acute pyelonephritis, acute allergic interstitial nephritis, or kidney allograft rejection. The histopathology of anti-TBM antibody disease is characterized by strong linear deposits of IgG with complement C3 along the proximal tubular cell basement membranes. The staining is restricted to proximal tubules. Currently, a kidney biopsy with these pathognomonic findings is the only diagnostic method. Serological testing and titers for anti-TBM antibodies are not clinically standardized. Our patient had pyelonephritis and possibly acute allergic interstitial nephritis as a result of nivolumab infusion. The kidney biopsy demonstrated dense interstitial infiltrates of neutrophil-rich interstitial inflammation, neutrophilic casts, and neutrophilic tubulitis consistent with acute pyelonephritis, as well as areas of mixed inflammation with lymphocytic tubulitis suggesting concurrent acute interstitial nephritis. The presence of linear IgG staining along proximal but not distal tubular basement membranes was diagnostic of anti-TBM antibody disease, favored to be due to both triggers. The patient was treated with discontinuation of nivolumab, intravenous antibiotics, and corticosteroids and was supported with hemodialysis. After 6 weeks, the patient’s kidney function recovered enough to discontinue hemodialysis and had significant renal improvement.
The Effect of High-Intensity Interval Training on Exercise Capacity in Patients with Coronary Artery Disease: A Systematic Review and Meta-Analysis
Authors: Li Siyi , Chen Xiankun , Jiao Huachen , Li Yan , Pan Guanghui , Yitao Xue
Published: April 2023

Background. The optimal exercise prescription for coronary artery disease (CAD) remains under debate. The aim of our meta-analysis is to investigate the efficacy of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) of coronary artery disease patients. Methods. Electronic databases were searched from their inception date until October 23, 2021, and the articles include randomized controlled trials. The mean differences and 95% confidence intervals were calculated, and heterogeneity was assessed using the I2 test. Results. The study standards were met by seventeen studies. The pooled studies included 902 patients. HIIT resulted in improvement in peak oxygen uptake (1.50 ml/kg/min, 95% confidence interval: 0.48 to 2.53, n = 853 patients, and low quality evidence) compared with MICT. There was no discernible difference between the individuals in the HIIT group and the MICT group in terms of systolic/diastolic blood pressure or peak/resting heart rate. Conclusion. This systematic review and meta-analysis reported the superiority of HIIT versus MICT in enhancing peak oxygen uptake in CAD patients.
Charles Bonnet Syndrome Related to a Pituitary Adenoma: A Case Study in a Tunisian Woman
Authors: Ghabi Haifa , Maamri Amira , Hajri Ahlem , Zalila Haifa
Published: April 2023

According to the International Statistical Classification of Diseases and Related Health Problems 11th Revision (ICD-11) definition, “Charles Bonnet Syndrome” (CBS) refers to the experience of complex visual hallucinations in a person who has experienced a partial or complete loss of vision. Pituitary adenoma is a rare situation that may be associated with CBS. We report a case of CBS in a Tunisian 44-year-old female with pituitary macroadenoma. The patient reported visual hallucinations which persisted after transsphenoidal adenomectomy. She had no prior psychiatric history. She did not take any medication that could produce hallucinations. After Olanzapine initiation, hallucinations were completely resolved. It is the first Tunisian case of CBS reported in English language. This peculiar condition seems to be under-recognized in our country. Clinicians should be aware that visual hallucinations may concern patients without psychiatric disorders.
Supplementary Table S5 from Regular Glucosamine Use May Have Different Roles in the Risk of Site-Specific Cancers: Findings from a Large Prospective Cohort
Authors: Li Fu-Xiao , Zhao Hou-Yu , Lin Teng-Fei , Jiang Yi-Wen , Liu Di , Wei Chang , Zhao Zi-Yi , Yang Zu-Yao , Sha Feng , Yang Zhi-Rong , Tang Jin-Ling
Published: April 2023

Supplementary Table S5 shows sensitivity analyses for the association between glucosamine use and risk of overall cancer after censoring certain cancers by gender.
Supplementary Figure S2 from Protein Kinase B (PKB/AKT) Protects IDH-Mutated Glioma from Ferroptosis via Nrf2
Authors: Liu Yang , Chou Fu-Ju , Lang Fengchao , Zhang Meili , Song Hua , Zhang Wei , Davis Dionne L. , Briceno Nicole J. , Zhang Yang , Cimino Patrick J. , Zaghloul Kareem A. , Gilbert Mark R. , Armstrong Terri S. , Yang Chunzhang
Published: April 2023

(A) Gene expression profiling showed the expression of GPX4 and SLC7A11 in IDH-mutated NHA cells (B) ROS-Glo assay measured the oxidative stress in IDH1WT and IDH1Mut NHA cells in response to ipatasertib (Ipa, 1 mM) treatment. (C) GSH, and GSSG level was measured in IDHWT and IDH1Mut NHA cells in response to Ipa (1 mM) treatment. GSH/GSSG ratio was calculated. (D) Immunoblotting analysis evaluated cleaved PARP in IDH1WT and IDH1Mut NHA cells with TMZ (200 mM) and/or Ipa (1mM) treatment. b-actin was used as an internal control. (E) Cell viability analysis on NHA IDHWT cells under TMZ (200 mM) and Ipa (1mM) treatment. **p < 0.01.
Figure S5 from An Enhancer Demethylator Phenotype Converged to Immune Dysfunction and Resistance to Immune Checkpoint Inhibitors in Clear-Cell Renal Cell Carcinomas
Authors: Lu Xiaofan , Vano Yann , Helleux Alexandra , Su Xiaoping , Lindner Véronique , Davidson Guillaume , Mouawad Roger , Spano Jean-Philippe , Rouprêt Morgan , Elaidi Reza , Compérat Eva , Verkarre Virginie , Sun Chengming , Chevreau Christine , Bennamoun Mostefa , Lang Hervé , Tricard Thibault , Cheng Wenxuan , Xu Li , Davidson Irwin , Yan Fangrong , Fridman Wolf Herman , Sautes-Fridman Catherine , Oudard Stéphane , Malouf Gabriel G.
Published: April 2023

Figure S5. Box violin plots showing the distribution of the methylation level of the TET1 associated promoter probe (i.e., cg23602092) in four cohorts and one cell line dataset with DNA methylation profiles where three of them had available normal samples.
Supplementary table 2 from Targeting MDSC Differentiation Using ATRA: A Phase I/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma
Authors: Tobin Richard P. , Cogswell Dasha T. , Cates Victoria M. , Davis Dana M. , Borgers Jessica S.W. , Van Gulick Robert J. , Katsnelson Elizabeth , Couts Kasey L. , Jordan Kimberly R. , Gao Dexiang , Davila Eduardo , Medina Theresa M. , Lewis Karl D. , Gonzalez Rene , McFarland Ross W. , Robinson William A. , McCarter Martin D.
Published: April 2023

All adverse events experienced by patients, including those unrelated to treatment
Supplementary Table S1 from Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma
Authors: Vasudev Naveen S. , Scelo Ghislaine , Glennon Kate I. , Wilson Michelle , Letourneau Louis , Eveleigh Robert , Nourbehesht Nazanin , Arseneault Madeleine , Paccard Antoine , Egevad Lars , Viksna Juris , Celms Edgars , Jackson Sharon M. , Abedi-Ardekani Behnoush , Warren Anne Y. , Selby Peter J. , Trainor Sebastian , Kimuli Michael , Cartledge Jon , Soomro Naeem , Adeyoju Adebanji , Patel Poulam M. , Wozniak Magdalena B. , Holcatova Ivana , Brisuda Antonin , Janout Vladimir , Chanudet Estelle , Zaridze David , Moukeria Anush , Shangina Oxana , Foretova Lenka , Navratilova Marie , Mates Dana , Jinga Viorel , Bogdanovic Ljiljana , Kovacevic Bozidar , Cambon-Thomsen Anne , Bourque Guillaume , Brazma Alvis , Tost Jörg , Brennan Paul , Lathrop Mark , Riazalhosseini Yasser , Banks Rosamonde E.
Published: April 2023

Clinical information and 12 gene mutation status for cohorts C1-C3
Data from Associating Immunotherapy and Targeted Therapies: Facts and Hopes
Authors: Ladoire Sylvain , Rébé Cédric , Ghiringhelli François
Published: April 2023

Abstract
Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1/PD-L1 (Programmed Death 1/Programmed Death-Ligand 1) axis, have modified the management of many types of cancer over the last 10 years. However, both intrinsic and acquired resistance are major clinical issues with these therapies, and only a few patients are cured by ICI monotherapy. To overcome resistance, the concept of combining ICIs with other therapies is emerging and supported by many preclinical trials. Besides associations of ICIs with chemotherapy or radiotherapy, now used in clinical practice, some targeted therapies have also been reported to influence immune response of patients against cancer cells, thus showing potential synergy with ICIs. In this review, we describe the preclinical and clinical advances to date in the use of these combination strategies.
Data from Enhanced Efficacy of IGF1R Inhibition in Pediatric Glioblastoma by Combinatorial Targeting of PDGFRα/β
Authors: Bielen Aleksandra , Perryman Lara , Box Gary M. , Valenti Melanie , de Haven Brandon Alexis , Martins Vanessa , Jury Alexa , Popov Sergey , Gowan Sharon , Jeay Sebastien , Raynaud Florence I. , Hofmann Francesco , Hargrave Darren , Eccles Suzanne A. , Jones Chris
Published: April 2023

Abstract
Pediatric glioblastoma (pGBM), although rare, is one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. We have identified IGF1R to be a potential therapeutic target in pGBM due to gene amplification and high levels of IGF2 expression in some tumor samples, as well as constitutive receptor activation in pGBM cell lines. To evaluate the therapeutic potential of strategies targeting the receptor, we have carried out in vitro and in vivo preclinical studies using the specific IGF1R inhibitor NVP-AEW541. A modest inhibitory effect was seen in vitro, with GI50 values of 5 to 6 μmol/L, and concurrent inhibition of receptor phosphorylation. Specific targeting of IGF1R with short interfering RNA decreased cell viability, diminished downstream signaling through phosphoinositide 3-kinase (PI3K), and induced G1 arrest, effects mimicked by NVP-AEW541, both in the absence and presence of IGF2. Hallmarks of PI3K inhibition were observed after treatment with NVP-AEW541 by expression profiling and Western blot analysis. Phospho–receptor tyrosine kinase (RTK) arrays showed phosphorylation of platelet-derived growth factor receptor (PDGFR) α/β in pGBM cells, suggesting coactivation of an alternative RTK pathway. Treatment of KNS42 with the PDGFR inhibitor imatinib showed additional effects targeting the mitogen-activated protein kinase pathway, and cotreatment of the PDGFR inhibitor imatinib with NVP-AEW541 resulted in a highly synergistic interaction in vitro and increased efficacy after 14 days therapy in vivo compared with either agent alone. These data provide evidence that inhibition of IGF1R, in combination with other targeted agents, may be a useful and novel therapeutic strategy in pGBM. Mol Cancer Ther; 10(8); 1407–18. ©2011 AACR.
Data from Metronomic Docetaxel in PRINT Nanoparticles and EZH2 Silencing Have Synergistic Antitumor Effect in Ovarian Cancer
Authors: Gharpure Kshipra M. , Chu Kevin S. , Bowerman Charles J. , Miyake Takahito , Pradeep Sunila , Mangala Selanere L. , Han Hee-Dong , Rupaimoole Rajesha , Armaiz-Pena Guillermo N. , Rahhal Tojan B. , Wu Sherry Y. , Luft J. Christopher , Napier Mary E. , Lopez-Berestein Gabriel , DeSimone Joseph M. , Sood Anil K.
Published: April 2023

Abstract
The purpose of this study was to investigate the antitumor effects of a combination of metronomic doses of a novel delivery vehicle, PLGA-PRINT nanoparticles containing docetaxel, and antiangiogenic mEZH2 siRNA incorporated into chitosan nanoparticles. In vivo dose-finding studies and therapeutic experiments were conducted in well-established orthotopic mouse models of epithelial ovarian cancer. Antitumor effects were determined on the basis of reduction in mean tumor weight and number of metastatic tumor nodules in the animals. The tumor tissues from these in vivo studies were stained to evaluate the proliferation index (Ki67), apoptosis index (cleaved caspase 3), and microvessel density (CD31). The lowest dose of metronomic regimen (0.5 mg/kg) resulted in significant reduction in tumor growth. The combination of PLGA-PRINT-docetaxel and CH-mEZH2 siRNA showed significant antitumor effects in the HeyA8 and SKOV3ip1 tumor models (P < 0.05). Individual as well as combination therapies showed significant antiangiogenic, antiproliferative, and proapoptotic effects, and combination therapy had additive effects. Metronomic delivery of PLGA-PRINT-docetaxel combined with CH-mEZH2 siRNA has significant antitumor activity in preclinical models of ovarian cancer. Mol Cancer Ther; 13(7); 1750–7. ©2014 AACR.
Data from Aerosol Administration of Phospho-Sulindac Inhibits Lung Tumorigenesis
Authors: Cheng Ka Wing , Wong Chi C. , Alston Ninche , Mackenzie Gerardo G. , Huang Liqun , Ouyang Nengtai , Xie Gang , Wiedmann Timothy , Rigas Basil
Published: April 2023

Abstract
Phospho-sulindac is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of phospho-sulindac might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of phospho-sulindac and evaluated the antitumor efficacy of inhaled phospho-sulindac in an orthotopic model of human non–small cell lung cancer (A549 cells). We found that administration by inhalation delivered high levels of phospho-sulindac to the lungs and minimized its hydrolysis to less active metabolites. Consequently, inhaled phospho-sulindac (6.5 mg/kg) was highly effective in inhibiting lung tumorigenesis (75%; P < 0.01) and significantly improved the survival of mice bearing orthotopic A549 xenografts. Mechanistically, phospho-sulindac suppressed lung tumorigenesis by (i) inhibiting EGF receptor (EGFR) activation, leading to profound inhibition of Raf/MEK/ERK and PI3K/AKT/mTOR survival cascades; (ii) inducing oxidative stress, which provokes the collapse of mitochondrial membrane potential and mitochondria-dependent cell death; and (iii) inducing autophagic cell death. Our data establish that inhalation delivery of phospho-sulindac is an efficacious approach to the control of lung cancer, which merits further evaluation. Mol Cancer Ther; 12(8); 1417–28. ©2013 AACR.
Data from NF-κB2/p52 Induces Resistance to Enzalutamide in Prostate Cancer: Role of Androgen Receptor and Its Variants
Authors: Nadiminty Nagalakshmi , Tummala Ramakumar , Liu Chengfei , Yang Joy , Lou Wei , Evans Christopher P. , Gao Allen C.
Published: April 2023

Abstract
Resistance of prostate cancer cells to the next-generation antiandrogen enzalutamide may be mediated by a multitude of survival signaling pathways. In this study, we tested whether increased expression of NF-κB2/p52 induces prostate cancer cell resistance to enzalutamide and whether this response is mediated by aberrant androgen receptor (AR) activation and AR splice variant production. LNCaP cells stably expressing NF-κB2/p52 exhibited higher survival rates than controls when treated with enzalutamide. C4-2B and CWR22Rv1 cells chronically treated with enzalutamide were found to express higher levels of NF-κB2/p52. Downregulation of NF-κB2/p52 in CWR22Rv1 cells chronically treated with enzalutamide rendered them more sensitive to cell growth inhibition by enzalutamide. Analysis of the expression levels of AR splice variants by quantitative reverse transcription PCR and Western blotting revealed that LNCaP cells expressing p52 exhibit higher expression of AR splice variants. Downregulation of expression of NF-κB2/p52 in VCaP and CWR22Rv1 cells by short hairpin RNA abolished expression of splice variants. Downregulation of expression of either full-length AR or the splice variant AR-V7 led to an increase in sensitivity of prostate cancer cells to enzalutamide. These results collectively demonstrate that resistance to enzalutamide may be mediated by NF-κB2/p52 via activation of AR and its splice variants. Mol Cancer Ther; 12(8); 1629–37. ©2013 AACR.
Data from Cytochrome P450 1B1 Gene Polymorphisms as Predictors of Anticancer Drug Activity: Studies with In vitro Models
Authors: Laroche-Clary Audrey , Morvan Valérie Le , Yamori Takao , Robert Jacques
Published: April 2023

Abstract
Cytochrome P450 1B1 (CYP1B1) is found in tumor tissue and is suspected to play a role in oncogenesis and drug resistance. CYP1B1 gene polymorphisms have been associated with the risk of developing lung and other cancers. They may be associated with tumor response to anticancer drugs. We have determined 4 frequent nonsynonymous gene polymorphisms of CYP1B1 in the human tumor cell lines panels of the National Cancer Institute (NCI) and the Japanese Foundation for Cancer Research (JFCR): rs10012 (R48G), rs1056827 (A119S), rs1056836 (L432V), and rs1800440 (N453S). Numerous anticancer drugs have been tested against these panels that offer the opportunity to detect associations between gene polymorphisms and drug sensitivity. CYP1B1 single nucleotide polymorphisms were in marked linkage disequilibrium. The L432V allelic variants were significantly associated with reduced sensitivity to DNA-interacting anticancer agents, alkylators, camptothecins, topoisomerase II inhibitors, and some antimetabolites. For instance, in the NCI panel, cell lines homozygous for the V432 allele were globally 2-fold resistant to alkylating agents (P = 5 × 10−10) and 4.5-fold to camptothecins (P = 6.6 × 10−9) than cell lines homozygous for the L432 allele. Similar features were exhibited by the JFCR panel. Cell lines homozygous for the V432 allele were globally less sensitive to DNA-interfering drugs than cell lines having at least 1 common allele. There was no significant association between mRNA expression of CYP1B1 and CYP1B1 genotype, and no significant association between CYP1B1 mRNA expression and drug cytotoxicity. These observations open the way to clinical studies exploring the role of CYP1B1 gene polymorphisms for predicting tumor sensitivity to chemotherapy. Mol Cancer Ther; 9(12); 3315–21. ©2010 AACR.
Data from Novel Neutralizing Hedgehog Antibody MEDI-5304 Exhibits Antitumor Activity by Inhibiting Paracrine Hedgehog Signaling
Authors: Michaud Neil R. , Wang Youzhen , McEachern Kristen A. , Jordan Jerold J. , Mazzola Anne Marie , Hernandez Axel , Jalla Sanjoo , Chesebrough Jon W. , Hynes Mark J. , Belmonte Matthew A. , Wang Lidong , Kang Jaspal S. , Jovanović Jelena , Laing Naomi , Jenkins David W. , Hurt Elaine , Liang Meina , Frantz Christopher , Hollingsworth Robert E. , Simeone Diane M. , Blakey David C. , Bedian Vahe
Published: April 2023

Abstract
The hedgehog pathway has been implicated in the tumorigenesis, tumor progression, and metastasis of numerous human cancers. We generated the first fully human hedgehog antibody MEDI-5304 and characterized its antitumor activity and preclinical toxicology. MEDI-5304 bound sonic hedgehog (SHH) and Indian hedgehog (IHH) with low picomolar affinity and neutralized SHH and IHH activity in cellular mGLI1 reporter assays. The antibody inhibited transcription of hedgehog target genes and osteoblast differentiation of C3H10T1/2 cells. We evaluated the activity of MEDI-5304 in vivo in model systems that allowed us to evaluate two primary hypotheses of hedgehog function in human cancer, paracrine signaling between tumor and stromal cells and cancer stem cell (CSC) self-renewal. MEDI-5304 displayed robust pharmacodynamic effects in stromal cells that translated to antitumor efficacy as a single agent in an HT-29/MEF coimplantation model of paracrine hedgehog signaling. MEDI-5304 also improved responses to carboplatin in the HT-29/MEF model. The antibody, however, had no effect as a single agent or in combination with gemcitabine on the CSC frequency or growth of several primary pancreatic cancer explant models. These findings support the conclusion that hedgehog contributes to tumor biology via paracrine tumor-stromal signaling but not via CSC maintenance or propagation. Finally, the only safety study finding associated with MEDI-5304 was ondontodysplasia in rats. Thus, MEDI-5304 represents a potent dual hedgehog inhibitor suitable for continued development to evaluate efficacy and safety in human patients with tumors harboring elevated levels of SHH or IHH. Mol Cancer Ther; 13(2); 386–98. ©2013 AACR.