bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of a novel SNAT2 (SLC38A2) inhibitor reveals synergy with glucose transport inhibition in cancer cells
Authors: Gauthier-Coles Gregory , Bröer Angelika , McLeod Malcolm Donald , George Amee J. , Hannan Ross D. , Bröer Stefan 
Published: September 2022

SNAT2 (SLC38A2) is a sodium-dependent neutral amino acid transporter, which is important for the accumulation of amino acids as nutrients, the maintenance of cellular osmolarity, and the activation of mTORC1. It also provides net glutamine for glutaminolysis and consequently presents as a potential target to treat cancer. A high-throughput screening assay was developed to identify new inhibitors of SNAT2 making use of the inducible nature of SNAT2 and its electrogenic mechanism. Using an optimized FLIPR membrane potential (FMP) assay, a curated scaffold library of 33934 compounds was screened to identify 3-(N-methyl (4-methylphenyl)sulfonamido)-N-(2-trifluoromethylbenzyl)thiophene-2-carboxamide as a potent inhibitor of SNAT2. In two different assays an IC50 of 0.8–3 µM was determined. The compound discriminated against the close transporter homologue SNAT1. MDA-MB-231 breast cancer and HPAFII pancreatic cancer cell lines tolerated the SNAT2 inhibitor up to a concentration of 100 µM but in combination with tolerable doses of the glucose transport inhibitor Bay-876, proliferative growth of both cell lines was halted. This points to synergy between inhibition of glycolysis and glutaminolysis in cancer cells.
Dose optimization of β-lactams antibiotics in pediatrics and adults: A systematic review
Authors: Haseeb Abdul , Faidah Hani Saleh , Alghamdi Saleh , Alotaibi Amal F. , Elrggal Mahmoud Essam , Mahrous Ahmad J. , Abuhussain Safa S. Almarzoky , Obaid Najla A. , Algethamy Manal , AlQarni Abdullmoin , Khogeer Asim A. , Saleem Zikria , Iqbal Muhammad Shahid , Ashgar Sami S. , Radwan Rozan Mohammad , Mutlaq Alaa , Fatani Nayyra , Sheikh Aziz 
Published: September 2022

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams.Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study.Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes.Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.
Comparison between conduction system pacing and cardiac resynchronization therapy in right bundle branch block patients
Authors: Strocchi Marina , Gillette Karli , Neic Aurel , Elliott Mark K. , Wijesuriya Nadeev , Mehta Vishal , Vigmond Edward J. , Plank Gernot , Rinaldi Christopher A. , Niederer Steven A. 
Published: September 2022

A significant number of right bundle branch block (RBBB) patients receive cardiac resynchronization therapy (CRT), despite lack of evidence for benefit in this patient group. His bundle (HBP) and left bundle pacing (LBP) are novel CRT delivery methods, but their effect on RBBB remains understudied. We aim to compare pacing-induced electrical synchrony during conventional CRT, HBP, and LBP in RBBB patients with different conduction disturbances, and to investigate whether alternative ways of delivering LBP improve response to pacing. We simulated ventricular activation on twenty-four four-chamber heart geometries each including a His-Purkinje system with proximal right bundle branch block (RBBB). We simulated RBBB combined with left anterior and posterior fascicular blocks (LAFB and LPFB). Additionally, RBBB was simulated in the presence of slow conduction velocity (CV) in the myocardium, left ventricular (LV) or right ventricular (RV) His-Purkinje system, and whole His-Purkinje system. Electrical synchrony was measured by the shortest interval to activate 90% of the ventricles (BIVAT-90). Compared to baseline, HBP significantly improved activation times for RBBB alone (BIVAT-90: 66.9 ± 5.5 ms vs. 42.6 ± 3.8 ms, p &lt; 0.01), with LAFB (69.5 ± 5.0 ms vs. 58.1 ± 6.2 ms, p &lt; 0.01), with LPFB (81.8 ± 6.6 ms vs. 62.9 ± 6.2 ms, p &lt; 0.01), with slow myocardial CV (119.4 ± 11.4 ms vs. 97.2 ± 10.0 ms, p &lt; 0.01) or slow CV in the whole His-Purkinje system (102.3 ± 7.0 ms vs. 75.5 ± 5.2 ms, p &lt; 0.01). LBP was only effective in RBBB cases if combined with anodal capture of the RV septum myocardium (BIVAT-90: 66.9 ± 5.5 ms vs. 48.2 ± 5.2 ms, p &lt; 0.01). CRT significantly reduced activation times in RBBB in the presence of severely slow RV His-Purkinje CV (95.1 ± 7.9 ms vs. 84.3 ± 9.3 ms, p &lt; 0.01) and LPFB (81.8 ± 6.6 ms vs. CRT: 72.9 ± 8.6 ms, p &lt; 0.01). Both CRT and HBP were ineffective with severely slow CV in the LV His-Purkinje system. HBP is effective in RBBB patients with otherwise healthy myocardium and Purkinje system, while CRT and LBP are ineffective. Response to LBP improves when LBP is combined with RV septum anodal capture. CRT is better than HBP only in patients with severely slow CV in the RV His-Purkinje system, while CV slowing of the whole His-Purkinje system and the myocardium favor HBP over CRT.
Criminal recidivism in offenders with and without intellectual disability sentenced to forensic psychiatric care in Sweden—A 17-year follow-up study
Authors: Edberg Hanna , Chen Qi , Andiné Peter , Larsson Henrik , Hirvikoski Tatja 
Published: September 2022

BackgroundOffenders with intellectual disability (ID) constitute a distinct subgroup of offenders with mental disorders. Regarding criminal recidivism, it is unclear whether or not offenders with ID in forensic psychiatric settings differ from offenders without ID. Factors associated with criminal recidivism among offenders with ID have been scarcely investigated.AimTo investigate the association between ID and criminal recidivism among offenders sentenced to forensic psychiatric care and to explore the impact of clinical, sociodemographic and offense variables.Materials and methodsWe conducted a retrospective cohort study based on Swedish nationwide registers. A total of 3,365 individuals being sentenced to forensic psychiatric care in Sweden in 1997–2013 were followed from the forensic psychiatric assessment until first reconviction, death, emigration, or 31 December 2013, whichever occurred first. Cox regression models compared rates of recidivism in individuals with and without ID. Impact of clinical, sociodemographic, and offense variables on risk of criminal recidivism was presented as hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsOut of 3,365 offenders sentenced to forensic psychiatric care, 259 (7.7%) were diagnosed with ID. During follow-up (0–17 years, median 6 years), one third (n = 1,099) of the study population relapsed into criminality, giving a recidivism rate of 50.5 per 1,000 person-years. We observed an association between ID and a decreased risk of recidivism (HR 0.8, 95% CI 0.6–1.0, p = 0.063), although this reached statistical significance only for the subgroup of male offenders (HR 0.8, 95% CI 0.6–1.0, p = 0.040) and not females (HR 1.0, 95% CI 0.6–1.8). ID offenders with concurrent ADHD tended to have a higher rate of recidivism (73.9 per 1,000 person-years, HR 1.2, 95% CI 0.6–2.4) than ID offenders without ADHD (42.5 per 1,000 person-years, HR 0.8, 95% CI 0.6–1.1). Amongst ID offenders, concurrent autism spectrum disorder, young age or male sex were not associated with recidivism, while previous criminal convictions were strongly associated with recidivism.ConclusionA diagnosis of ID was associated with a lower risk of criminal recidivism among male offenders sentenced to forensic psychiatric care. The association between ADHD and recidivism among ID offenders highlights eligible focus areas in the management of offenders with ID.
The mirror mechanism in schizophrenia: A systematic review and qualitative meta-analysis
Authors: Valizadeh Amir , Mbwogge Mathew , Rasouli Yazdi Anita , Hedayati Amlashi Nazanin , Haadi Ainaaz , Shayestefar Monir , Moassefi Mana 
Published: September 2022

BackgroundMirror neuron system (MNS) consists of visuomotor neurons that are responsible for the mirror neuron activity (MNA), meaning that each time an individual observes another individual performing an action, these neurons encode that action, and are activated in the observer's cortical motor system. Previous studies report its malfunction in autism, opening doors to investigate the underlying pathophysiology of the disorder in a more elaborate way and coming up with new rehabilitation methods. The study of MNA function in schizophrenia patients has not been as frequent and conclusive as in autism. In this research, we aimed to evaluate the functional integrity of MNA and the microstructural integrity of MNS in schizophrenia patients.MethodsWe included case-control studies that have evaluated MNA in schizophrenia patients compared to healthy controls using a variety of objective assessment tools. In August 2022, we searched Embase, PubMed, and Web of Science for eligible studies. We used an adapted version of the NIH Quality Assessment of Case-Control Studies tool to assess the quality of the included studies. Evidence was analyzed using vote counting methods of the direction of the effect and was tested statistically using the Sign test. Certainty of evidence was assessed using CERQual.ResultsWe included 32 studies for the analysis. Statistical tests revealed decreased MNA (p = 0.002) in schizophrenia patients. The certainty of the evidence was judged to be moderate. Investigations of heterogeneity revealed a possible relationship between the age and the positive symptoms of participants in the included studies and the direction of the observed effect.DiscussionThis finding contributes to gaining a better understanding of the underlying pathophysiology of the disorder by revealing its possible relation to some of the symptoms in schizophrenia patients, while also highlighting a new commonality with autism.Systematic review registrationPROSPERO identifier: CRD42021236453.
Adverse childhood experiences growing up in East or West Germany or abroad
Authors: Schulz Ann-Christin , Kasinger Christoph , Beutel Manfred , Fegert Jörg M. , Clemens Vera , Brähler Elmar 
Published: September 2022

BackgroundAdverse childhood experiences (ACEs) are potentially traumatic events that occur before the age of 18. The term encompasses various adverse childhood experiences, e.g., physical, psychological, and sexual abuse, physical and psychological neglect, and family dysfunction. Prevalence estimates for a broad spectrum of ACEs against the background of where childhood and adolescence were spent are scarcely available in Germany. This study examines the frequencies of adverse childhood experiences, considering growing up in East or West Germany or abroad and interacting with different age cohorts and gender.MethodsA total of 5,018 individuals (51.4% female) aged 14 years and older were retrospectively assessed on adverse childhood experiences using questionnaires “adverse childhood experiences” (ACE). Logistic regression models were used to analyze the association between birth cohort, gender, and where a person grew up. Descriptive statistics and univariate analyses were used to calculate frequencies, proportions, and unadjusted associations for each variable.Results37.4% (N = 1,878) of respondents reported experiencing at least one form of ACE. Individuals who grew up abroad report significantly more adverse childhood experiences than individuals in East or West Germany. Men and women who grew up in East Germany reported a lower rate of ACEs. We found significant effects for all predictors: Where childhood and adolescence were predominantly spent, year of birth, and gender. Significant differences in the prevalence of adverse childhood experiences within the gender groups were only found for sexual and physical abuse and substance dependence in the household.ConclusionThe results suggest that the socio-political context plays an essential role in the experience of adverse childhood experiences, both in frequency and risk. Thus, child abuse and neglect studies should increasingly focus on societal risk and protection mechanisms.
Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic
Authors: Mao Wei , Li Fujuan , Li Bin , Li Yunxia , Zhang Xiaolan , Ou Zhengjie , Liu Shuai , Zhao Dan 
Published: September 2022

ObjectivesWomen with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib.MethodsThe survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL.ResultsA total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress.ConclusionsThis study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.
Autism and anorexia nervosa: Longitudinal prediction of eating disorder outcomes
Authors: Leppanen Jenni , Sedgewick Felicity , Halls Daniel , Tchanturia Kate 
Published: September 2022

BackgroundRecently, elevated levels of autistic features and autism diagnoses have been reported among people with anorexia nervosa (AN). In clinical settings high levels of autistic features have been linked to more complex, highly comorbid illness presentation and poorer treatment outcome. This study aimed to examine whether autistic features predict AN symptom profile in long term.MethodsAltogether 118 women with lived experience of AN completed two autism assessments at time 1, the Autism Diagnostic Observation Schedule (ADOS) and the short version of the Autism Quotient (AQ10). Measures assessing AN symptom profile, including eating disorders symptoms, anxiety, depression, OCD symptoms, and Body Mass Index (BMI), were also recorded. The symptom profile measures were administered again 6 months and 2 years later. We conducted two analyses to examine the extent to which the ADOS and AQ10 scores predicted broad AN symptom profile at each three time points.ResultsOverall, high levels of autistic features were consistently associated with worse psychological symptoms, but not BMI, across all time points. Both the analysis using baseline ADOS scores and self-reported AQ10 scores showed similar pattern.ConclusionThe present findings consolidate previously reported associations between autistic features and worse psychological outcome among people with AN. The findings also suggest that self-report measures may be sufficient for assessing the impact of autistic features on illness outcome among people with AN. Importantly, the study highlights the need for development and further investigation of neurodiversity accommodations in the treatment of AN.
Do private health providers adhere to National Tuberculosis Guideline while assigning treatment outcome? Findings from a lower middle-income country
Authors: Adepoju Victor Abiola , Adejumo Olusola Adedeji , Adepoju Oluwatoyin Elizabeth , Adeniyi Marius Olusola , Etuk Victoria , Nzekwe Iheoma , Inegbeboh Jude O. , Adelekan Ademola , Oladimeji Olanrewaju 
Published: September 2022

BackgroundTreatment success rate is an important indicator to measure the performance of the National Tuberculosis Program (NTP). There are concerns about the quality of outcome data from private facilities engaged by NTP. Adherence of private providers of tuberculosis care to NTP guideline while assigning treatment outcomes to patients is rarely investigated. We aimed to determine whether Lagos private for-profit (PFP) and private not-for-profit (PNFP) facilities adhere to domestic TB guideline while assigning treatment outcome and the availability of periodic sputum acid-fast bacilli (AFB) results.MethodA retrospective review of facility treatment register and treatment cards of TB patients managed between January and December 2016 across 10 private directly observed treatment short-course (DOTS) facilities involved in the public–private mix (PPM) in Lagos, Nigeria. The study took place between January and June 2019.ResultsOf the 1,566 patients, majority (60.7%) were male, &gt;30 years (50.2%), HIV-negative (88.4%), and attended PNFP (78.5%). The reported treatment success rate (TSR) was 84.2% while the actual TSR was 53.8%. In total, 91.1, 77.6, and 70.3% of patients had sputum acid-fast bacilli (AFB) at 2/3, month 5, and month 6, respectively, while 68.6% had all the three sputum AFB in the register. Healthcare workers (HCWs) were adherent in assigning treatment outcome for 65.6% of TB patients while 34.4% of patients were assigned incorrect treatment outcomes. Most variations between reported and actual treatment outcomes were found with cured (17%) and completed (13.4%). Successful and unsuccessful outcomes were overreported by 30.4% and 4.1%, respectively. DOTS providers in private facilities with available TB guideline (OR 8.33, CI 3.56–19.49, p &lt; 0.0001) and PNFP facility (OR 4.42, CI 1.91–10.3, p = 0.001) were more likely to adhere to National TB Guideline while assigning TB treatment outcome.ConclusionFrontline TB providers in Lagos private hospitals struggled with assigning correct treatment outcome for TB patients based on NTBLCP guideline. Increased access to all the periodic follow-up AFB tests for TB patients on treatment and availability of National TB Guideline for referencing could potentially improve the adherence of private TB service providers while assigning TB treatment outcomes.
Cost-efficient analysis of a portable low field magnetic resonance imaging system for prostate cancer diagnosis
Authors: Sze Christina , Cheema Zaid , Laviana Aaron , Margolis Daniel , Costa Daniel N. , Satya Poorvi , Nacev Aleksander , Kumar Dinesh , Venkataraman Srirama S. , Chughtai Bilal 
Published: September 2022

PurposeMagnetic resonance imaging (MRI)-guided procedures are typically performed under high magnetic field strengths (1.5-3 Tesla) and are expensive. Recently, technological progress has led to MRIs that are low-cost but similarly high performing despite lower field strengths (58-74mT). Our purpose was to evaluate the cost-efficiency of implementing a low-field MRI for targeted prostate cancer biopsy.Materials and methodsWe utilized time-driven activity-based costing (TDABC) to establish the overall costs based on cost rates and total times for every step. Thorough literature searches and consultations with two board certified radiologists, the process maps were created, and the duration of each step was determined by experience and previously published data. A sensitivity cost analysis was also performed to create several cost scenarios for the low-field MRI system.ResultsTotal procedure times, performed under moderate sedation, were 61 ± 14.5 mins and 57 ± 23 mins for transperineal targeted biopsy (TPB) with low-field MRI and in-bore MRI-guided transrectal biopsy (IB-TBx) with high-field MRI. In the low-field MRI pathway, 61% of intra-operative time was spent on patient preparation and performing the prebiopsy MRI, however, this step did not require a urologist or radiologist expertise, subsequently keeping costs lower. A sensitivity analysis of the low-field MRI cost at 5% to 50% (in 5% increments) of a high-field MRI produced a difference from $888.13 to $879.18 favoring the lower-field system, respectively.ConclusionsA portable, low field, office-based MRI system offers a cost-efficient alternative to the high-field MRI. Further studies assessing cost effectiveness while taking into consideration sampling accuracy are needed.
General practice-based cancer research publications: a bibliometric analysis 2013–2019
Authors: Milley Kristi , Chima Sophie , Karnchanachari Napin , McNamara Mairead , Druce Paige , Emery Jon 
Published: September 2022

BackgroundGeneral practice plays a critical role in the prevention, diagnosis, management, and survivorship care of patients with cancer. Mapping research outputs over time provides valuable insights into the evolving role of general practice in cancer care.AimTo describe and compare the distribution of cancer in general practice research publications by country, cancer type, area of the cancer continuum, author sex, and journal impact factor.Design and settingA bibliometric analysis using a systematic approach to identify publications.MethodMEDLINE and Embase databases were searched for studies published between 2013 and 2019, which reported on cancer in general practice. Included studies were mapped to the cancer continuum framework. Descriptive statistics were used to present data from the included studies.ResultsA total of 2798 publications were included from 714 journals, spanning 79 countries. The publication rate remained stable over this period. Overall, the US produced the most publications (n= 886, 31.7%), although, per general population capita, Denmark produced nearly 10 times more publications than the US (20.0 publications per million compared with 2.7 publications per million). Research across the cancer continuum varied by country, but, overall, most studies focused on cancer screening, diagnosis, and survivorship. More than half of included studies used observational study designs (n= 1523, 54.4%). Females made up 66.5% (n= 1304) of first authors, but only 47.0% (n= 927) of last authors.ConclusionCancer in general practice is a stable field where research is predominantly observational. There is geographical variation in the focus of cancer in general practice research, which may reflect different priorities and levels of investment between countries. Overall, these results support future consideration of how to improve under-represented research areas and the design, conduct, and translation of interventional research.