bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular dissociation grading on biopsies of pulmonary squamous cell carcinoma provides prognostic information across all stages and is congruent with resection specimen grading
Authors: Jesinghaus Moritz , Boxberg Melanie , Schmitt Maxime , Kriegsmann Mark , Harms Alexander , Lang Corinna , Muley Thomas , Winter Hauke , Kriegsmann Katharina , Warth Arne , Stenzinger Albrecht , Denkert Carsten , Hoffmann Hans , Safi Seyer , Weichert Wilko 
Published: September 2022

AbstractGrading of squamous cell carcinomas (SCCs) based on tumour budding and cell nest size has been termed cellular dissociation grading (CDG) and was suggested as a robust outcome predictor when assessed in biopsies and resections of various extrapulmonary SCCs. In pulmonary SCC (pSCC), this has so far been shown only for resected cancers. As most lung cancers are inoperable, it is of utmost importance to clarify whether the prognostic impact of CDG is retained in the biopsy setting. Two independent pSCC biopsy cohorts from Munich (n = 134, non‐resected) and Heidelberg (n = 135, resected) were assessed. Tumour budding and cell nest size measures were assembled into the three‐tiered CDG system (G1–G3). Data were correlated with clinicopathological parameters and overall‐ (OS), disease‐specific‐ (DSS), and disease‐free survival (DFS). Interobserver variability and concordance between biopsy and resection specimen were also investigated. CDG was highly congruent between biopsy and resection specimens (κ = 0.77, p < 0.001). In both pSCC cohorts, biopsy‐derived CDG strongly impacted on OS, DSS, and DFS (e.g. DFS: p < 0.001). In multivariate survival analyses, CDG remained a stage independent predictor of survival in both cohorts (DFS: p < 0.001 respectively; hazard ratio Munich cohort: CDG‐G2: 4.31, CDG‐G3; 5.14; Heidelberg cohort: CDG‐G2: 5.87, CDG‐G3: 9.07). Interobserver agreement for CDG was almost perfect (κ = 0.84, p < 0.001). We conclude that assessment of CDG based on tumour budding and cell nest size is feasible on pSCC biopsies and harbours stage independent prognostic information in resectable as well as non‐resectable pSCC. Integration of this grading approach into clinicopathological routine should be considered.
How External Electric Field Modulates the Rotation Energy Profiles of Dipolar Dopants Inside C70: A Theoretical Interpretation with Electrostatic Shielding Effect Incorporated
Authors: Peng Xinru , Chen Li , Dang Jingshuang , Wang Changwei , Mo Yirong 
Published: September 2022

AbstractEndohedral fullerenes, which can switch between distinct states with different geometries when triggered by external electric fields (EFs), can be used as logical devices at the molecular scale. However, the movement of electrons around fullerenes exerts an electrostatic shielding effect which alleviates the Coulomb force experienced by endohedral dopants, and thus must be properly evaluated for better elucidating the switching mechanism. Here we introduced new components to the energy decomposition scheme based on the block‐localized wavefunction method (i. e., BLW‐ED), to incorporate the shielding effect explicitly. We analyzed the external EF‐driven rotation of enclosed dipolar molecules inside C70 and evaluated the magnitudes of shielding in terms of the gradients of electrostatic potential and energy. In the absence of external EF, intrinsic rotational barriers are dominated by the Pauli exchange repulsion between enclosed molecules and C70. When an external EF was applied, computations showed that only about 18% of external EFs can penetrate into the cage and interact with dipolar molecules. Thus, the shielding effect dramatically reduces the energy contribution originated from the interaction between endohedral dopants and external EFs. BLW‐ED analyses were further performed to inspect the effect of external EFs on the potential energy surfaces associated with the molecular rotation processes. Indeed, the interaction between penetrated EFs and enclosed molecules can still govern the orientational preferences of dipolar molecules and lower the rotational barrier for some dipolar molecules. But for other molecules, both the intrinsic electrostatic interaction and the Pauli repulsion respond to external EFs more sensitively and rule the changes of barrier heights and orientational preferences.
Pharmacogenomic Testing and Depressive Symptom Remission: A Systematic Review and Meta‐Analysis of Prospective, Controlled Clinical Trials
Authors: Brown Lisa C. , Stanton Joseph D. , Bharthi Kanika , Maruf Abdullah Al , Müller Daniel J. , Bousman Chad A. 
Published: September 2022

Pharmacogenomic (PGx) testing has emerged as a compelling strategy that clinicians can use to inform antidepressant medication selection and dosing, but the clinical efficacy of this strategy has been questioned. We systematically reviewed and meta‐analyzed clinical trials for an association between the use of PGx‐guided antidepressant therapy and depressive symptom remission in patients with major depressive disorder (MDD). We included prospective, controlled clinical trials published in English up to July 12, 2022. Data extraction and synthesis adhered to the 2020 Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Each trial was assessed for risk of bias and a random‐effects model was used to estimate pooled risk ratios. Thirteen trials comprising 4,767 patients were analyzed, including 10 randomized controlled trials, and three open label trials. Across all included trials, those that received PGx‐guided antidepressant therapy (n = 2,395) were 1.41 (95% confidence interval (CI) = 1.15–1.74, P = 0.001) more likely to achieve remission compared with those that received unguided antidepressant therapy (n = 2,372). Pooled risk ratios for randomized controlled trials and open label trials were 1.46 (95% CI: 1.13–1.88) and 1.26 (95% CI = 0.84–1.88), respectively. These results suggest that PGx‐guided antidepressant therapy is associated with a modest but significant increase in depressive symptom remission in adults with MDD. Efforts to address the heterogeneity in PGx test composition (i.e., genes and alleles tested) and accompanying prescribing recommendations across trials will likely reduce the uncertainty about the efficacy of PGx‐guided antidepressant therapy in the literature.
Evaluation of Glutaminolysis in T Cells
Authors: Tajima Masaki , Strober Warren 
Published: September 2022

AbstractThe activity of living cells is necessarily dependent on the amount of available bioenergy. In T cells, the latter is mainly derived from ATP, a molecular energy “coin” generated by one of several metabolic processes that differ in their ability to satisfy energy demand. Thus, whereas naïve or quiescent T cells efficiently utilize oxidative phosphorylation to generate ATP, T cells subjected to antigenic stimulation followed by clonal expansion and cytokine production meet their increased need for energy by supplementing ATP generation by oxidative phosphorylation with ATP generation by glycolysis. Yet additional need for ATP can be met by other basic biologic sources of energy such as glutamine, an amino acid that is metabolized through a process called glutaminolysis to result in end products that flows into the TCA cycle and augment ATP generation by oxidative phosphorylation. It is now possible to track the dominant energy supplying processes (i.e., the ATP generation process) in differentiating or activated T cells in a real‐time manner. Here, we provide one element of such tracking by describing protocols for the assessment of the contribution of glutaminolysis to overall ATP production within different T cell subsets. © 2022 Wiley Periodicals LLC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.Basic Protocol 1: Evaluation of the role of glutaminolysis during T cell activation/differentiationBasic Protocol 2: Evaluation of the role of glutaminolysis in T cell responses utilizing glutaminolysis inhibitorsBasic Protocol 3: Evaluation of the effect of glutaminolysis on cellular oxidative phosphorylation/glycolysis
Stability: Concept, relevance, inducing and maintaining it
Authors: Sahni Kanika 
Published: September 2022

AbstractVitiligo is an autoimmune disease resulting in destruction of melanocytes which leads to depigmented patches on the skin. An assessment of disease activity and/or stability is important for many reasons, one of them being planning surgical intervention. Though there are sufficient studies in the literature exploring the clinical, biochemical, and molecular predictors of disease stability, there still exists ambiguity in many of these aspects. There are no longitudinal prospective cohort studies to assess the course of vitiligo and it is difficult to predict the status of stability of the disease with certainty. This review focuses on the clinical features which can help a clinician judge whether the disease is progressive in a patient being planned for surgical intervention. Subsequently, there is also a discussion on tools including ultraviolet light photography, imaging software, and dermoscopy in accurately assessing the stability of disease. This is followed by a review of the literature on the biochemical, serological, microscopic, and ultrastructural findings in active versus static disease. The review ends with interventions for inducing and maintaining stability in this enigmatic disease.
Characteristics and long‐term survival of patients with left ventricular non‐compaction cardiomyopathy
Authors: Demir Emre , Bayraktaroğlu Selen , Çinkooğlu Akın , Candemir Aytaç , Candemir Yeşim B. , Öztürk Rıza O. , Dadaş Ömer F. , Orman Mehmet N. , Zoghi Mehdi , Akıllı Azem , Ceylan Naim , Gürgün Cemil , Nalbantgil Sanem 
Published: September 2022

AbstractAimsLeft ventricular non‐compaction cardiomyopathy (LVNC) is a poorly understood entity resulting in heart failure. Whether it is a distinct form of cardiomyopathy or an anatomical phenotype is a subject of discussion. The current diagnosis is based on morphologic findings by comparing the compacted to non‐compacted myocardium. The study aimed to compare demographic and prognostic variables of patients with dilated cardiomyopathy (DCM) and LVNC. Emphasis was given to cardiac magnetic resonance (CMR) imaging analysis. Data on survival were also assessed.Methods and resultsWe retrospectively evaluated the characteristics and outcomes of 262 non‐ischaemic cardiomyopathy patients with LVNC and DCM phenotypes. Petersen's CMR criteria of non‐compacted to the compacted myocardial ratio 2.3 were used to diagnose LVNC. The primary endpoint was a composite endpoint of major adverse cardiovascular events comprising cardiovascular‐related death, left ventricular assisted device implantation, or heart transplantation. A total of 262 patients with CMR data were included in the study. One hundred fifty‐five patients who fulfilled CMR criteria were diagnosed as LVNC. CMR findings revealed that LVNC patients had higher left ventricular end‐diastolic (137.2 ± 51.6, 116.8 ± 44.6, P = 0.002) and systolic volume index (98.4 ± 49.5, 85.9 ± 42.7, P = 0.049). Cardiac haemodynamics, cardiac output (5.61 ± 2.03, 4.96 ± 1.83; P = 0.010), stroke volume (73.9 ± 28.8, 65.1 ± 25.1; P = 0.013), and cardiac index (2.85 ± 1.0, 2.37 ± 0.72; P < 0.0001), were higher in LVNC patients. Of all the 249 patients, 102 (40.9%) patients demonstrated late gadolinium enhancement (LGE). According to Petersen's criteria, the Kaplan–Meier survival outcome did not reveal significant differences (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: [0.89–2.63], P = 0.11). The presence or pattern of LGE did not show significant importance for endpoint‐free survival. Most of the sub‐epicardial LGE pattern was found in LVNC patients (94.4%). When receiver operator characteristics analysis was applied to NC/C ratio to discriminate the primary endpoint, a higher NC/C ratio of 2.57 was associated with adverse events (HR: 1.90, 95% CI: [1.12–3.24], P = 0.016).ConclusionsOur study questions the criteria being used for the diagnosis of LVNC. Further evaluation of CMR variables and association of these findings with demographic variables and survival is mandatory.
Heart failure during the COVID‐19 pandemic: clinical, diagnostic, management, and organizational dilemmas
Authors: Palazzuoli Alberto , Metra Marco , Collins Sean P. , Adamo Marianna , Ambrosy Andrew P. , Antohi Laura E. , Ben Gal Tuvia , Farmakis Dimitrios , Gustafsson Finn , Hill Loreena , Lopatin Yuri , Tramonte Francesco , Lyon Alexander , Masip Josep , Miro Oscar , Moura Brenda , Mullens Wilfried , Radu Razvan I. , Abdelhamid Magdy , Anker Stefan , Chioncel Ovidiu 
Published: September 2022

AbstractThe coronavirus 2019 (COVID‐19) infection pandemic has affected the care of patients with heart failure (HF). Several consensus documents describe the appropriate diagnostic algorithm and treatment approach for patients with HF and associated COVID‐19 infection. However, few questions about the mechanisms by which COVID can exacerbate HF in patients with high‐risk (Stage B) or symptomatic HF (Stage C) remain unanswered. Therefore, the type of HF occurring during infection is poorly investigated. The diagnostic differentiation and management should be focused on the identification of the HF phenotype, underlying causes, and subsequent tailored therapy. In this framework, the relationship existing between COVID and onset of acute decompensated HF, isolated right HF, and cardiogenic shock is questioned, and the specific management is mainly based on local hospital organization rather than a standardized model. Similarly, some specific populations such as advanced HF, heart transplant, patients with left ventricular assist device (LVAD), or valve disease remain under investigated. In this systematic review, we examine recent advances regarding the relationships between HF and COVID‐19 pandemic with respect to epidemiology, pathogenetic mechanisms, and differential diagnosis. Also, according to the recent HF guidelines definition, we highlight different clinical profile identification, pointing out the main concerns in understudied HF populations.
Theory of plastic mechanism control: A new approach for the optimization of seismic resistant steel frames
Authors: Montuori Rosario , Nastri Elide , Piluso Vincenzo 
Published: September 2022

AbstractThis paper presents an important improvement in seismic design of structures based on the application of the Theory of Plastic Mechanism Control (TPMC). TPMC was originally proposed in the ‘90s requiring an iterative algorithm and upgraded in 2015 leading to the so‐called closed form solution. In the recent years, TPMC has shown its value as an effective design procedure which can be applied to any structural typology. Moreover, it has been used as a code competitor design tool in important RFCS founded research projects confirming its effectiveness, simplicity, and suitability to any structural typology. The aim of the TPMC is the design of structures able to exhibit at collapse a global type mechanism. The TPMC was originally based on the extension of the kinematic theorem of plastic collapse to the concept of mechanism equilibrium curve, working in the plane (being α the multiplier of the seismic forces and δ the top sway displacement). The novelty of this work is improvement of the design procedure by working in the plane, being θ the plastic rotation. This new TPMC approach, namely TPMC(θ), has demonstrated to be as reliable as the former approach, thus leading to structures able to develop a collapse mechanism of global type but with the optimization of the structure using lighter columns. The effectiveness of the new procedure has been confirmed by both pushover and dynamic non‐linear analyses.
Integrated energy generation and storage systems for low‐power device applications
Authors: Kansal Sakshi , Priya Surbhi , Porwal Shivam , Chandra Amreesh , Singh Trilok 
Published: September 2022

AbstractThe growing demand for alternative renewable sources of energy apart from conventional fossil fuels gathered attention for exploring solar, wind, tidal geothermal energy, etc. However, the intermittent energy supply constraint the full‐fledged utilization of these energy sources and hence, to address this issue, a new technique of integrated energy generation and storage systems (IEGSSs) is extensively explored. In this review, we have comprehensively discussed the ongoing research on various IEGSSs, and their different integration techniques constituting solar cells, batteries, and supercapacitors. This article also highlighted certain challenges faced by the IEGSSs which restrict their full‐fledged application. Finally, some prospects that can flourish their utilization in the field of various portable devices, wearables, off‐grid electrification, and IoT sensors for smart cities are discussed.
Steatosis, HBV‐related HCC, cirrhosis, and HBsAg seroclearance: A systematic review and meta‐analysis
Authors: Mao Xianhua , Cheung Ka Shing , Peng Chengzhi , Mak Lung‐Yi , Cheng Ho Ming , Fung James , Peleg Noam , Leung Howard H.‐W. , Kumar Rajneesh , Lee Jeong‐Hoon , Shlomai Amir , Yuen Man‐Fung , Seto Wai‐Kay 
Published: September 2022

Background and Aims:
NAFLD and chronic hepatitis B (CHB) infection are common etiologies of HCC. The impact of hepatic steatosis on HCC in CHB, as well as its relationship with the development of cirrhosis, fibrosis, and HBsAg seroclearance, remains controversial.

Approach and Results:
Data from observational studies were collected through PubMed, EMBASE, and the Cochrane Library from inception to February 1, 2022. Outcomes of interest included the association of hepatic steatosis with HCC, cirrhosis, advanced fibrosis, and HBsAg seroclearance, expressed in terms of pooled ORs. Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A total of 34 studies with 68,268 patients with CHB were included. Hepatic steatosis was associated with higher odds of HCC (OR, 1.59; 95% CI, 1.12–2.26; I
2 = 72.5%), with the association remaining consistent in Asia (OR, 1.56; 95% CI, 1.08–2.25), studies with a median follow‐up duration of ≥5 years (OR, 2.82; 95% CI, 1.57–5.08), exclusion of alcohol use (OR, 1.71; 95% CI, 1.01–2.91), and biopsy‐proven steatosis (OR, 2.86; 95% CI, 1.61–5.06), although no significant association was noted among nucleos(t)ide analogue–treated patients (OR, 1.05; 95% CI, 0.62–1.77). Steatosis was associated with the development of cirrhosis (OR, 1.52; 95% CI, 1.07–2.16; I
2 = 0%) and HBsAg seroclearance (OR, 2.22; 95% CI, 1.58–3.10; I
2 = 49.0%).

Conclusions:
Hepatic steatosis was associated with an increased risk of HCC and cirrhosis among patients with CHB but with a higher chance of achieving a functional cure, highlighting the importance of identifying concomitant steatosis in CHB.
Vasor: Accurate prediction of variant effects for amino acid substitutions in multidrug resistance protein 3
Authors: Behrendt Annika , Golchin Pegah , König Filip , Mulnaes Daniel , Stalke Amelie , Dröge Carola , Keitel Verena , Gohlke Holger 
Published: September 2022

Abstract
The phosphatidylcholine floppase multidrug resistance protein 3 (MDR3) is an essential hepatobiliary transport protein. MDR3 dysfunction is associated with various liver diseases, ranging from severe progressive familial intrahepatic cholestasis to transient forms of intrahepatic cholestasis of pregnancy and familial gallstone disease. Single amino acid substitutions are often found as causative of dysfunction, but identifying the substitution effect in in vitro studies is time and cost intensive. We developed variant assessor of MDR3 (Vasor), a machine learning‐based model to classify novel MDR3 missense variants into the categories benign or pathogenic. Vasor was trained on the largest data set to date that is specific for benign and pathogenic variants of MDR3 and uses general predictors, namely Evolutionary Models of Variant Effects (EVE), EVmutation, PolyPhen‐2, I‐Mutant2.0, MUpro, MAESTRO, and PON‐P2 along with other variant properties, such as half‐sphere exposure and posttranslational modification site, as input. Vasor consistently outperformed the integrated general predictors and the external prediction tool MutPred2, leading to the current best prediction performance for MDR3 single‐site missense variants (on an external test set: F1‐score, 0.90; Matthew's correlation coefficient, 0.80). Furthermore, Vasor predictions cover the entire sequence space of MDR3. Vasor is accessible as a webserver at https://cpclab.uni‐duesseldorf.de/mdr3_predictor/ for users to rapidly obtain prediction results and a visualization of the substitution site within the MDR3 structure. The MDR3‐specific prediction tool Vasor can provide reliable predictions of single‐site amino acid substitutions, giving users a fast way to initially assess whether a variant is benign or pathogenic.
The introduction of a value‐based reimbursement programme—Alignment and resistance among healthcare providers
Authors: Eriksson Thérèse , Levin Lars‐Åke , Nedlund Ann‐Charlotte 
Published: September 2022

AbstractReimbursement programmes are used to manage care through financial incentives. However, their effects are mixed and the programmes can motivate behaviour that goes against professional values. Value‐based reimbursement programmes may better align professional values with financial incentives. The aim of this study is to analyse if and how healthcare providers adapt their practices to a value‐based reimbursement programme that combines bundled payment with performance‐based payment. Forty‐one semi‐structured interviews were conducted with representatives from healthcare providers within spine surgery in Sweden. Data were analysed using thematic analysis with an abductive approach and a conceptual framework based on neo‐institutional theory. Healthcare providers were positive to the idea of a value‐based reimbursement programme. However, during its introduction it became evident that some aspects were easier to adapt to than others. The bundled payment provided a more comprehensive picture of the patients' needs but to an increased administrative burden. Due to the financial impact of the bundled payment, healthcare providers tried to decrease the amount of post‐discharge care. The performance‐based payment was appreciated. However, the lack of financial impact and transparency in how the payment was calculated caused providers to neglect it. Healthcare providers adapted their practices to, but also resisted aspects of the value‐based reimbursement programme. Resistance was mainly caused by lack of understanding of how to interpret and act on new information. Providers had to face unfamiliar situations, which they did not know how to handle. Better IT‐facilitation and clearer definition of related care is needed to strengthen the value‐based reimbursement programme among healthcare providers. A value‐based reimbursement programme seems to better align professional values with financial incentives.