bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the family doctor system on the continuity of care for diabetics in urban China: a difference-in-difference analysis
Authors: Liu Xinyi , Zhang Luying , Chen Wen 
Published: February 2023

ObjectivesOur study aimed to examine whether the family doctor system can improve continuity of care for patients with diabetes.DesignRegistry-based, population-level longitudinal cohort study.SettingLinked data from the administrative Health Information System and the Health Insurance Claim Databases in a sample city in eastern China.Participants30 451 insured patients who were diagnosed with diabetes before January 2015 in the sample city, with ≥2 outpatient visits per year during 2014–2017. Diabetics in the intervention group had been registered with family doctor teams from 2015 to 2017, while those who had not registered were taken as the control group.InterventionsThe family doctor system was established in China mainly to strengthen primary care and rebuild referral systems. Residents were encouraged to register with family doctors to obtain continuous health management especially for chronic disease management.Outcome measuresContinuity of care was measured by the Continuity of Care Index (COCI), Usual Provider Continuity Score (UPCS) and Sequential Continuity of Care Index (SECON) in 2014–2017.ResultsCOCI, UPCS and SECON of all diabetics in this study increased between 2014 and 2017. A difference-in-difference approach was applied to measure the net effect of the family doctor system on continuity of care. Our model controlled for demographic and socioeconomic characteristics, and severity of disease at baseline. Compared with the control group, diabetics registered with family doctors obtained an average 0.019 increase in COCI (SE 0.002) (p<0.01), a 0.016 increase in UPCS (SE 0.002) (p<0.01) and a 0.018 increase in SECON (SE 0.002) (p<0.01).ConclusionThis study provides evidence that the family doctor system can effectively improve continuity of care for patients with diabetes, which has substantial policy implications for further primary care reform in China.
Defining the temporal relationship between the skin microbiome, immune response and skin barrier function during flare and resolution of atopic dermatitis: protocol of a Danish intervention study
Authors: Rønnstad Amalie Thorsti Møller , Bay Lene , Ruge Iben Frier , Halling Anne-Sofie , Fritz Blaine Gabriel , Jakaša Ivone , Luiten Rosalie , Kezic Sanja , Thomsen Simon Francis , Bjarnsholt Thomas , Thyssen Jacob P. 
Published: February 2023

IntroductionLesional skin of atopic dermatitis (AD) is often colonised byStaphylococcus aureusand the bacterial abundance increases during a flare. However, the role ofS. aureusand the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.Methods and analysisThis clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologousS. aureus, staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.Ethics and disseminationThe scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov:NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.Trial registration numberNCT05578482, EudraCT 2021-006883-2.
Price and affordability of key essential medicines for children in Sri Lanka, a lower-middle-income country: comparison of two national cross-sectional surveys done 8 years apart
Authors: Sri Ranganathan Shalini , Navaratinaraja Thiyahiny Sunil , Balasubramaniam Ramasamy , Beneragama Hemantha 
Published: February 2023

ObjectiveTo describe the price and affordability of key essential medicines for children in the private sector in Sri Lanka in 2017/2018, and compare the findings with 2009 data.DesignNational cross-sectional descriptive survey using the WHO/Health Action International medicine price methodology.Setting and participantsData were collected from a representative sample of 54 private sector pharmacies selected from all 9 provinces in Sri Lanka using a multistage clustered approach.Main outcomesMedian price ratio (MPR) and affordability of originator brand (OB) and lowest priced generics (LPG) of 25 key essential medicines for children.ResultsThe median MPR was 2.69 for OBs and 1.45 for LPGs compared with 3.7 and 1.35 in 2009. MPR of OB of all but one (chlorphenamine syrup) were higher than that of the LPG. MPR-OB>5 was observed for ceftriaxone injection, amoxicillin capsule, mebendazole chewable tablet and metronidazole tablet. This was documented in 2009 as well except for amoxicillin capsule. Prices of LPGs of seven medicines (amoxicillin capsule, amoxicillin suspension, clotrimazole cream, mebendazole chewable tablet, metronidazole tablet) were estimated as excessive (MPR ≥2.5) compared with chlorphenamine syrup, clotrimazole topical cream, ibuprofen syrup and paracetamol syrup in 2009. Compared with 2009, MPRs of OBs of 8 medicines and LPGs of 12 medicines were higher in 2017/2018. Compared with 2009, no change in affordability was noted except for asthma, which has been assessed as affordable in 2017/2018. Standard drug therapy for mild lower respiratory tract infections and acute gastroenteritis remained affordable, and treating epilepsy with carbamazepine syrup remained unaffordable.ConclusionEconomic access to key essential medicines for children has not improved in Sri Lanka in the 8 years’ time since the initial survey in 2009.
Effect of ICU care bundles on long-term patient-relevant outcomes: a scoping review
Authors: Paul Nicolas , Ribet Buse Elena , Knauthe Anna-Christina , Nothacker Monika , Weiss Björn , Spies Claudia D 
Published: February 2023

ObjectiveCare bundles are considered a key tool to improve bedside quality of care in the intensive care unit (ICU). We explored their effect on long-term patient-relevant outcomes.DesignSystematic literature search and scoping review.Data sourcesWe searched PubMed, Embase, CINAHL, APA PsycInfo, Web of Science, CDSR and CENTRAL for keywords of intensive care, care bundles, patient-relevant outcomes, and follow-up studies.Eligibility criteriaOriginal articles with patients admitted to adult ICUs assessing bundle implementations and measuring long-term (ie, ICU discharge or later) patient-relevant outcomes (ie, mortality, health-related quality of life (HrQoL), post-intensive care syndrome (PICS), care-related outcomes, adverse events, and social health).Data extraction and synthesisAfter dual, independent, two-stage selection and charting, eligible records were critically appraised and assessed for bundle type, implementation strategies, and effects on long-term patient-relevant outcomes.ResultsOf 2012 records, 38 met inclusion criteria; 55% (n=21) were before–after studies, 21% (n=8) observational cohort studies, 13% (n=5) randomised controlled trials, and 11% (n=4) had other designs. Bundles pertained to sepsis (n=11), neurocognition (n=6), communication (n=4), early rehabilitation (n=3), pharmacological discontinuation (n=3), ventilation (n=2) or combined bundles (n=9). Almost two-thirds of the studies reported on survival (n=24), 45% (n=17) on care-related outcomes (eg, discharge disposition), and 13% (n=5) of studies on HrQoL. Regarding PICS, 24% (n=9) assessed cognition, 13% (n=5) physical health, and 11% (n=4) mental health, up to 1 year after discharge. The effects of bundles on long-term patient-relevant outcomes was inconclusive, except for a positive effect of sepsis bundles on survival. The inconclusive effects may have been due to the high risk of bias in included studies and the variability in implementation strategies, instruments, and follow-up times.ConclusionsThere is a need to explore the long-term effects of ICU bundles on HrQoL and PICS. Closing this knowledge gap appears vital to determine if there is long-term patient value of ICU bundles.
Quasi normal modes of hairy black holes at higher-order WKB approach
Authors: Avalos R. , Contreras E. 
Published: February 2023

AbstractIn this work, we implement the 13th order semi-analytical WKB method to explore the stability of hairy black holes obtained in the framework of Gravitational Decoupling. In particular, we perform a detailed analysis of the frequencies of the quasi-normal modes as a function of the primary hair of the solutions with the aim to bound their values. We explore a broad interval in a step of 0.1 of the hair parameters. We find that except for some cases where the method is expected to have poor accuracy, all the solutions seem to be stable and the role played by the primary hair is twofold: to modulate the damping factor of the perturbation and to decrease the frequency of its oscillation.
Quantum encryption of superposition states with quantum permutation pad in IBM quantum computers
Authors: Perepechaenko Maria , Kuang Randy 
Published: February 2023

AbstractWe present an implementation of Kuang and Bettenburg’s Quantum Permutation Pad (QPP) used to encrypt superposition states. The project was conducted on currently available IBM quantum systems using the Qiskit development kit. This work extends previously reported implementation of QPP used to encrypt basis states and demonstrates that application of the QPP scheme is not limited to the encryption of basis states. For this implementation, a pad of 56 2-qubit Permutation matrices was used, providing 256 bits of entropy for the QPP algorithm. An image of a cat was used as the plaintext for this experiment. The plaintext was randomized using a classical XOR function prior to the state preparation procedure. To create corresponding superposition states, we applied a novel operator defined in this paper. These superposition states were then encrypted using QPP, with 2-qubit Permutation Operators, producing superposition ciphertext states. Due to the lack of a quantum channel, we omitted the transmission and executed the decryption procedure on the same IBM quantum system. If a quantum channel existed, the superposition ciphertext states could be transmitted as qubits, and be directly decrypted on a different quantum system. We provide a brief discussion of the security, although the focus of the paper remains on the implementation. Previously we have demonstrated QPP operating in both classical and quantum computers, offering an interesting opportunity to bridge the security gap between classical and quantum systems. This work broadens the applicability of QPP for the encryption of basis states as well as superposition states. We believe that quantum encryption schemes that are not limited to basis states will be integral to a secure quantum internet, to reduce vulnerabilities introduced by using two separate algorithms for secure communication between a quantum and a classical computer.
Hopf instability of a Rayleigh–Taylor unstable thin film heated from the gas side
Authors: Bestehorn Michael , Oron Alexander 
Published: February 2023

AbstractA thin liquid film located on the underside of a horizontal solid substrate can be stabilized by the Marangoni effect if the liquid is heated at its free surface. Applying long-wave approximation and projecting the velocity and temperature fields onto a basis of low-order polynomials, we derive a dimension-reduced set of three coupled evolution equations where nonlinearities of both the Navier–Stokes and the heat equation are included. We find that in a certain range of fluid parameters and layer depth, the first bifurcation from the motionless state is oscillatory which sets in with a finite but small wave number. The oscillatory branch is determined using a linear stability analysis of the long-wave model, but also by solving the linearized original hydrodynamic equations. Finally, numerical solutions of the reduced nonlinear model equations in three spatial dimensions are presented.
Dysregulation of Mitochondrial Translation Caused byCBFBDeficiency Cooperates with Mutant PIK3CA and Is a Vulnerability in Breast Cancer
Authors: Malik Navdeep , Kim Young-Im , Yan Hualong , Tseng Yu-Chou , du Bois Wendy , Ayaz Gamze , Tran Andy D. , Vera-Ramirez Laura , Yang Howard , Michalowski Aleksandra M. , Kruhlak Michael , Lee Maxwell , Hunter Kent W. , Huang Jing 
Published: February 2023

AbstractUnderstanding functional interactions between cancer mutations is an attractive strategy for discovering unappreciated cancer pathways and developing new combination therapies to improve personalized treatment. However, distinguishing driver gene pairs from passenger pairs remains challenging. Here, we designed an integrated omics approach to identify driver gene pairs by leveraging genetic interaction analyses of top mutated breast cancer genes and the proteomics interactome data of their encoded proteins. This approach identified that PIK3CA oncogenic gain-of-function (GOF) and CBFB loss-of-function (LOF) mutations cooperate to promote breast tumor progression in both mice and humans. The transcription factor CBFB localized to mitochondria and moonlighted in translating the mitochondrial genome. Mechanistically, CBFB enhanced the binding of mitochondrial mRNAs to TUFM, a mitochondrial translation elongation factor. Independent of mutant PI3K, mitochondrial translation defects caused by CBFB LOF led to multiple metabolic reprogramming events, including defective oxidative phosphorylation, the Warburg effect, and autophagy/mitophagy addiction. Furthermore, autophagy and PI3K inhibitors synergistically killed breast cancer cells and impaired the growth of breast tumors, including patient-derived xenografts carrying CBFB LOF and PIK3CA GOF mutations. Thus, our study offers mechanistic insights into the functional interaction between mutant PI3K and mitochondrial translation dysregulation in breast cancer progression and provides a strong preclinical rationale for combining autophagy and PI3K inhibitors in precision medicine for breast cancer.Significance:CBFB-regulated mitochondrial translation is a regulatory step in breast cancer metabolism and synergizes with mutant PI3K in breast cancer progression.
Venadaparib Is a Novel and Selective PARP Inhibitor with Improved Physicochemical Properties, Efficacy, and Safety
Authors: Lee Myongjae , Je In-Gyu , Kim Jeong Eun , Yoo Yeongran , Lim Jong-Ha , Jang Eunhye , Lee Yoonsuk , Song Dong Keun , Moon An-Na , Kim Jeong-Ah , Jeong Jinah , Park Joon-Tae , Lee Jung Woo , Yang Ji-Hoon , Hong Chang-Hee , Park Sun-Young , Park Young-Whan , Baek Nam Seok , Lee Sungsook , Ha Kyoung Soo , Choi SungKu , Lee Won Sik 
Published: February 2023

AbstractPARP inhibitors have been approved by the FDA for use in the treatment of patients with ovarian, breast, pancreatic, and prostate cancers. PARP inhibitors show diverse suppressive effects on PARP family members and PARP-DNA trapping potency. These properties are associated with distinct safety/efficacy profiles. Here, we report the nonclinical characteristics of venadaparib (also known as IDX-1197 or NOV140101), a novel potent PARP inhibitor. The physiochemical properties of venadaparib were analyzed. Furthermore, the efficacy of venadaparib against PARP enzymes, PAR formation, and PARP trapping activities, and growth inhibition of cell lines with BRCA mutations were evaluated. Ex vivo and in vivo models were also established to study pharmacokinetics/pharmacodynamics, efficacy, and toxicity. Venadaparib specifically inhibits PARP-1 and -2 enzymes. Oral administration of venadaparib HCl at doses above 12.5 mg/kg significantly reduced tumor growth in the OV_065 patient-derived xenograft model. Intratumoral PARP inhibition remained at over 90% until 24 hours after dosing. Venadaparib had wider safety margins than olaparib. Notably, venadaparib showed favorable physicochemical properties and superior anticancer effects in homologous recombination-deficient in vitro and in vivo models with improved safety profiles. Our results suggest the possibility of venadaparib as a next-generation PARP inhibitor. On the basis of these findings, phase Ib/IIa studies on the efficacy and safety of venadaparib have been initiated.
SGN-CD228A Is an Investigational CD228-Directed Antibody–Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models
Authors: Mazahreh Rebecca , Mason Marsha L. , Gosink John J. , Olson Devra J. , Thurman Robert , Hale Christopher , Westendorf Lori , Pires Thomas A. , Leiske Christopher I. , Carlson Markus , Nguyen Liem T. , Cochran Julia H. , Okeley Nicole M. , Yumul Roma , Jin Steven , Stone Ivan J. , Sahetya Disha , Nesterova Albina , Allred Sean , Hensley Kelly M. , Hu Rachael , Lawrence Robert , Lewis Timothy S. , Sandall Sharsti 
Published: February 2023

AbstractSGN-CD228A is an investigational antibody–drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of a humanized antibody, hL49, with high specificity and affinity for CD228 that is stably conjugated to 8 molecules of the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. We performed comprehensive IHC studies, which corroborated published RNA sequencing data and confirmed low CD228 expression in normal tissues and high expression in several cancers, including melanoma, squamous non–small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. SGN-CD228A was efficiently internalized in various tumor cell types, and its cytotoxic activity was dependent on CD228 expression and internalization and intrinsic sensitivity to the MMAE payload. Compared with the valine-citrulline dipeptide linker, the novel glucuronide linker increased the cellular retention of MMAE in vitro and conferred improved antitumor activity against melanoma cell lines in vitro and in vivo. In addition, SGN-CD228A was active across melanoma, TNBC, and NSCLC cell line- and patient-derived xenograft models with heterogeneous antigen expression. In vivo, CD228 expression was important for response to SGN-CD228A but was not well correlated across all tumor types, suggesting that other factors associated with ADC activity are important. Overall, SGN-CD228A is a CD228-directed, investigational ADC that employs innovative technology and has compelling preclinical antitumor activity. SGN-CD228A is investigated in a Phase I clinical trial (NCT04042480) in patients with advanced solid tumors.
Evolution of the Southwest Drought Learning Network: Collective Response to Exceptional Drought
Authors: Elias Emile , Fuchs Brian , Lisonbee Joel , Bernadt Tonya , Martinez Viktorya , Haigh Tonya 
Published: February 2023

Abstract
The 2018 exceptional drought over the Colorado Plateau motivated unprecedented responses by individuals and organizations. Some of these responses made clear that proactive adaptive measures were fundamental to drought resilience. Climate service organizations (CSOs) supporting and observing these responses realized the utility of a network to share and document successful drought responses. In February 2020, a small group of CSOs and resource managers (RMs) met to envision the Southwest Drought Learning Network (DLN) to align with other existing efforts, but with the specific goal of enabling peer-to-peer learning to build resilience to future droughts. Since then, the network has grown into five organized teams focused on specific aspects of building drought resilience. Team activities include sharing case studies to help others learn from past experiences, hosting monthly drought briefings that introduce drought data and management tools, identifying information needed to support critical management decisions, innovating and sharing new and traditional drought monitoring technologies, and building drought resilience with indigenous communities. The network allows for collaboration and leveraging partner resources and strengths. The DLN website (https://dln.swclimatehub.info/) hosts more information about network teams and activities. This innovative network continues to grow in response to management needs and water scarcity in the region. For the benefit of others who may be considering a similar network and supporting peer-to-peer learning, we document the history, process, and lessons learned regarding the Southwest DLN.
Trends in Comprehensive Thoracic Case Experience Among General Surgery Residents in the Modern Integrated Cardiothoracic Residency Era: Review of Twenty Years of Resident Case Logs
Authors: Blitzer David , Benintende Andrew J. , Nemeth Samantha , Kurlansky Paul , Antkowiak Mark , Fischkoff Katherine , Argenziano Michael , Takayama Hiroo 
Published: February 2023

Background Thoracic surgery training among general surgery residents in the United States is regulated by the Accreditation Council for Graduate Medical Education (ACGME) to ensure exposure to subspecialty fields during residency. Thoracic surgery training has changed over time with the placement of work hour restrictions, the emphasis on minimally invasive surgery, and increased subspecialization of training like integrated six-year cardiothoracic surgery programs. We aim to investigate how these changes over the past twenty years have affected thoracic surgery training among general surgery residents. Methods ACGME general surgery resident case logs from 1999 to 2019 were reviewed. Data included exposure to the thorax via thoracic, cardiac, vascular, pediatric, trauma, and alimentary tract procedures. Cases from the above categories were consolidated to determine the comprehensive experience. Descriptive statistics were performed over four 5-year Eras (Era 1:1999-2004, Era 2: 2004-2009, Era 3: 2009-2014, Era 4: 2014-2019). Results Between Era 1 and Era 4, there was an increase in thoracic surgery experience (37.6 ± 1.03 vs 39.3 ± .64; P = .006). The mean total thoracic experience for thoracoscopic, open, and cardiac procedures was 12.89 ± 3.76, 20.09 ± 2.33, and 4.98 ± 1.28, respectively. There was a difference between Era 1 and Era 4 in thoracoscopic (8.78 ± .961 vs 17.18 ± .75; P < .001) and open thoracic experience (22 ± .97 vs 17.06 ± .88; P < .001), and a decrease in thoracic trauma procedures (3.7 ± .06 vs 3.2 ± .32; P = .03). Discussion Over twenty years there has been a similar, to slight increase in thoracic surgery exposure among general surgery residents. The changes seen in thoracic surgery training reflect the overall movement of surgery towards minimally invasive surgery.