bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics-Pharmacodynamics Modeling and Evaluation of Tumor Response to Bortezomib Proteasome Inhibitor in Waldenstrom Macroglobulinemia
Authors: Munir Anum , Fazal Sahar , Bhatti Aamer Iqbal , Sajjad Bilawal 
Published: February 2023

Background:
Waldenstrom’s macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is a type of non-Hodgkin’s lymphoma in which the malignant cells produce many macroglobulin proteins. It originates from B cells and develops in the bone marrow, where Wm cells combine to produce distinct types of blood cells, resulting in reduced volumes of red blood cells, white blood cells, and platelets, making it harder for the body to fight diseases. Chemoimmunotherapy is being used for the clinical management of WM, but new targeted agents, the BTK inhibitor ibrutinib and the proteasome inhibitor bortezomib, have shown significant improvements in patients with relapsed/refractory WM. However, given its effectiveness, drug resistance and relapse are normal, and there is little research on the pathways responsible for drug effects on the tumor.

Methods:
In this study, Pharmacokinetics-pharmacodynamic simulations were done to assess the effect of the proteasome inhibitor bortezomib on the tumor. For this purpose, the Pharmacokinetics-pharmacodynamic model was developed. The model parameters were determined and calculated using the Ordinary Differential Equation solver toolbox and the least-squares function. Pharmacokinetic profiles and pharmacodynamic analysis were performed to determine the change in tumor weight associated with the use of proteasome inhibitors.

Results:
Bortezomib and ixazomib have been found to reduce tumor weight briefly, but once the dose is reduced, the tumor begins to grow again. Carfilzomib and oprozomib had better results, and rituximab reduced tumor weight more effectively.

Conclusion:
Once validated, it is proposed that a combination of selected drugs can be evaluated in the laboratory to treat WM.
Hepatic mitochondrial NAD+ transporter SLC25A47 activates AMPKα mediating lipid metabolism and tumorigenesis
Authors: Cheng Lili , Deepak R.N.V. Krishna , Wang Guoqiang , Meng Ziyi , Tao Lei , Xie Mengqing , Chi Wenna , Zhang Yuming , Yang Mingming , Liao Yilie , Chen Ruiqun , Liang Yu , Zhang Junyu , Huang Yuedong , Wang Weihua , Guo Zhiying , Wang Yunfang , Lin Jiandie D. , Fan Hao , Chen Ligong 
Published: February 2023

Background & Aims:
SLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism.

Approach & Results:
In the treatment of hepatocytes with metformin, we found that metformin can transcriptionally activate the expression of Slc25a47, which is required for AMP-activated protein kinase α (AMPKα) phosphorylation. Slc25a47-deficient mice had increased hepatic lipid content, triglycerides, and cholesterol levels, and we found that Slc25a47 deficiency suppressed AMPKα phosphorylation and led to an increased accumulation of nuclear SREBPs, with elevated fatty acid and cholesterol biosynthetic activities. Conversely, when Slc25a47 was overexpressed in mouse liver, AMPKα was activated and resulted in the inhibition of lipogenesis. Moreover, using a diethylnitrosamine-induced mouse HCC model, we found that the deletion of Slc25a47 promoted HCC tumorigenesis and development through the activated mammalian target of rapamycin cascade. Employing homology modeling of SLC25A47 and virtual screening of the human metabolome database, we demonstrated that NAD+ was an endogenous substrate for SLC25A47, and the activity of NAD+-dependent sirtuin 3 declined in Slc25a47-deficient mice, followed by inactivation of AMPKα.

Conclusions:
Our findings reveal that SLC25A47, a hepatocyte-specific mitochondrial NAD+ transporter, is one of the pharmacological targets of metformin and regulates lipid homeostasis through AMPKα, and may serve as a potential drug target for treating NAFLD and HCC.
Standard vs total keratometry for intraocular lens power calculation in cataract surgery combined with DMEK
Authors: Khan Asher , Rangu Neal , Murphy David A. , Cooke David L. , Siatkowski Rhea L. , Mittal Aman , Wendelstein Jascha A. , Riaz Kamran M. 
Published: February 2023

Purpose:
To compare the prediction accuracy of standard keratometry (K) and total keratometry (TK) for intraocular lens (IOL) power calculation in eyes undergoing combined cataract surgery and Descemet membrane endothelial keratoplasty (triple DMEK).

Setting:
Tertiary care academic referral center.

Design:
Retrospective case series.

Methods:
Review of 83 eyes (63 patients) that underwent triple DMEK between 2019 and 2021. Biometry measurements were obtained using a swept-source optical biometer (IOLMaster 700). 63 eyes were used for statistical analysis. Mean error, mean absolute error (MAE), SD, median absolute error, maximum absolute error, root mean squared prediction error, and the percentage of eyes within prediction errors of ±0.50 diopters (D) and ±1.00 D were calculated for 9 multivariate and third-generation formulas using K and TK values (Barrett Universal II, Yeo EVO 2.0, Cooke K6, Kane, Pearl-DGS, Haigis, Holladay 1, Hoffer Q, and SRK/T). Formulas were additionally tested by using the prediction for an IOL power 1 D below the IOL used (IOLup1D).

Results:
For all formulas, MAE was lower for K than for TK by an average of 0.21 D. The lowest MAE value observed was 0.67 D for “adjusted” SRK/T using K, and the highest MAE values observed were 1.24 D and 1.24 D for nonadjusted Hoffer Q and Haigis using TK, respectively. Overall, lower MAE values were observed for multivariate formulas and SRK/T.

Conclusions:
In triple DMEK eyes, the prediction accuracy of K was higher than that of TK. The most accurate formulas were SRK/T and multivariate formulas using K with the IOLup1D adjustment.
Use, Durability, and Risks for Discontinuation of Initial and Subsequent Biologics in a Large Pediatric-Onset IBD Cohort
Authors: Kaplan Jess L. , Liu Chunyan , King Eileen C. , Bass Julie A. , Patel Ashish S. , Tung Jeanne , Chen Shiran , Lissoos Trevor , Candela Ninfa , Saeed Shehzad , Colletti Richard B. ,   for the ImproveCareNow Network
Published: February 2023

Background:
Biologic medications are recommended for treatment of moderately-to-severely active Crohn disease (CD) or ulcerative colitis (UC) in children. However, many patients require sequential biologic treatment because of nonresponse or loss of response to the initial biologic.

Methods:
We analyzed pediatric inflammatory bowel disease (IBD) data from the ImproveCareNow Network registry between May 2006 and September 2016, including time to biologic initiation, choice of first subsequent biologics, biologic durability, and reasons for discontinuation.

Results:
Of 17,649 patients with IBD [CD: 12,410 (70%); UC: 5239 (30%)], 7585 (43%) were treated with a biologic agent before age 18 (CD: 50%; UC: 25%). Biologic treatment was more likely for CD than UC (odds ratio, 3.0; 95% CI: 2.8–3.2; P < 0.0001). First biologic agents for all patients were anti-tumor necrosis factor agents (88% infliximab, 12% adalimumab). Probability of remaining on the first biologic was significantly higher in CD than UC (P < 0.0001). First biologics were discontinued because of loss of response (39%), intolerance (23%), and nonresponse (19%). In univariate analysis, factors associated with discontinuation of first and/or second biologics in CD include colonic-only disease, corticosteroid use, upper gastrointestinal tract involvement, and clinical and biochemical markers of severe disease. Biologic durability improved with later induction date.

Conclusions:
Treatment with biologic medications is common in pediatric IBD. Patients with CD are more likely to receive biologics, receive biologics earlier in disease course, and remain on the first biologic longer than patients with UC. Multiple factors may predict biologic durability in children with IBD.
Costs, Health Benefits, and Cost-Effectiveness of Chlamydia Screening and Partner Notification in the United States, 2000–2019: A Mathematical Modeling Analysis
Authors: Rönn Minttu M. , Li Yunfei , Gift Thomas L. , Chesson Harrell W. , Menzies Nicolas A. , Hsu Katherine , Salomon Joshua A. 
Published: February 2023

Background
Chlamydia remains a significant public health problem that contributes to adverse reproductive health outcomes. In the United States, sexually active women 24 years and younger are recommended to receive annual screening for chlamydia. In this study, we evaluated the impact of estimated current levels of screening and partner notification (PN), and the impact of screening based on guidelines on chlamydia associated sequelae, quality adjusted life years (QALYs) lost and costs.

Methods
We conducted a cost-effectiveness analysis of chlamydia screening, using a published calibrated pair formation transmission model that estimated trends in chlamydia screening coverage in the United States from 2000 to 2015 consistent with epidemiological data. We used probability trees to translate chlamydial infection outcomes into estimated numbers of chlamydia-associated sequelae, QALYs lost, and health care services costs (in 2020 US dollars). We evaluated the costs and population health benefits of screening and PN in the United States for 2000 to 2015, as compared with no screening and no PN. We also estimated the additional benefits that could be achieved by increasing screening coverage to the levels indicated by the policy recommendations for 2016 to 2019, compared with screening coverage achieved by 2015.

Results
Screening and PN from 2000 to 2015 were estimated to have averted 1.3 million (95% uncertainty interval [UI] 490,000–2.3 million) cases of pelvic inflammatory disease, 430,000 (95% UI, 160,000–760,000) cases of chronic pelvic pain, 300,000 (95% UI, 104,000–570,000) cases of tubal factor infertility, and 140,000 (95% UI, 47,000–260,000) cases of ectopic pregnancy in women. We estimated that chlamydia screening and PN cost $9700 per QALY gained compared with no screening and no PN. We estimated the full realization of chlamydia screening guidelines for 2016 to 2019 to cost $30,000 per QALY gained, compared with a scenario in which chlamydia screening coverage was maintained at 2015 levels.

Discussion
Chlamydia screening and PN as implemented in the United States from 2000 through 2015 has substantially improved population health and provided good value for money when considering associated health care services costs. Further population health gains are attainable by increasing screening further, at reasonable cost per QALY gained.
Book Chapter (Kluwer) - Preprint Version.pdf
Authors: Aliu Armando , Aliu Dorian 
Published: February 2023

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<p>The research aims to analyze the impact of the World Trade Organization on enhancing the legitimacy of global economic governance within the scope of the WTO law. The world economic outlook and macro-data indicators demonstrate that the convergence of interests amongst state actors and nonstate actors reinforces the efficiency of Bretton Woods institutions, such as the World Bank and the International Monetary Fund. The objective of this study is to highlight the fact that the WTO has vital efforts to strengthen the legitimacy of the global economic governance mechanism and liberalize economic activity in the world economic system. In a more liberalized transnational relations environment, the activities, operations, and efforts of nonstate actors provide a ground to stabilize economic cooperation and sustainable development. From a macro perspective, the study aims to monitor the first five-year period of the global financial crisis (2008-2013) and present the descriptive statistics and intercorrelations for 36 OECD countries. The research results indicate that 36 states’ governments should develop sustainable solutions to issues related to GDP, social security, and public / private expenditure in global economic governance platforms. In collaboration with governments, the WTO’s role is vital to cooperate with ILO and enhance its legitimacy and efficiency in labor relations, industrial relations, and employment protection. The research results illustrate that global economic governance has been reshaped by a ‘duality of global governance approach’ (i.e., a <em>de facto</em> G2: US-China relations), and the principles of global economic development have been reconstructed during the transition period from the Washington consensus to the Beijing consensus (G2 hegemony), competitively.</p>
Feasibility and Safety of a “Shared Care” Model in Complex Hepatopancreatobiliary Surgery
Authors: Lee Alex , Al-Arnawoot Ahmed , Rajendran Luckshi , Lamb Tyler , Turner Anastasia , Reid Morgann , Rekman Janelle , Mimeault Richard , Abou Khalil Jad , Martel Guillaume , Bertens Kimberly A. , Balaa Fady 
Published: February 2023

Objective:To determine the safety of a fully functioning shared care model (SCM) in hepatopancreatobiliary surgery through evaluating outcomes in pancreaticoduodenectomy.Background:SCMs, where a team of surgeons share in care delivery and resource utilization, represent a surgeon-level opportunity to improve system efficiency and peer support, but concerns around clinical safety remain, especially in complex elective surgery.Methods:Patients who underwent pancreaticoduodenectomy between 2016 and 2020 were included. Adoption of shared care was demonstrated by analyzing shared care measures, including the number of surgeons encountered by patients during their care cycle, the proportion of patients with different consenting versus primary operating surgeon (POS), and the proportion of patients who met their POS on the day of surgery. Outcomes, including 30-day mortality, readmission, unplanned reoperation, sepsis, and length of stay, were collected from the institution’s National Surgical Quality Improvement Program (NSQIP) database and compared with peer hospitals contributing to the pancreatectomy-specific NSQIP collaborative.Results:Of the 174 patients included, a median of 3 surgeons was involved throughout the patients’ care cycle, 69.0% of patients had different consenting versus POS and 57.5% met their POS on the day of surgery. Major outcomes, including mortality (1.1%), sepsis (5.2%), and reoperation (7.5%), were comparable between the study group and NSQIP peer hospitals. Length of stay (10 day) was higher in place of lower readmission (13.2%) in the study group compared with peer hospitals.Conclusions:SCMs are feasible in complex elective surgery without compromising patient outcomes, and wider adoption may be encouraged.
Uncinate Duct Dilatation Predicts Additional Risk for High-Grade Dysplasia or Invasive Carcinoma Among Fukuoka-Positive Intraductal Papillary Mucinous Neoplasms
Authors: Yang Alan Z. , Kongboonvijit Sasiprang , Fernandez-del Castillo Carlos F. , Fong Zhi Ven , Zelga Piotr J. , Ferrone Cristina R. , Lillemoe Keith D. , Kambadakone Avinash , Qadan Motaz 
Published: February 2023

Objective:
To determine whether uncinate duct dilatation (UDD) increases the risk of high-grade dysplasia or invasive carcinoma (HGD/IC) in Fukuoka-positive intraductal papillary mucinous neoplasms (IPMNs).

Background:
Though classified as a branch duct, the uncinate duct is the primary duct of the pancreatic ventral anlage. We hypothesized that UDD, like main duct dilatation, confers additional risk for HGD/IC.

Methods:
A total of 467 patients met inclusion criteria in a retrospective cohort study of surgically resected IPMNs at the Massachusetts General Hospital. We used multivariable logistic regression to analyze the association between UDD (defined as ≥4 mm) and HGD/IC, controlling for Fukuoka risk criteria. In a secondary analysis, the modeling was repeated in the 194 patients with dorsal branch duct IPMNs (BD-IPMNs) in the pancreatic neck, body, or tail.

Results:
Mean age at surgery was 70, and 229 (49%) patients were female. In total, 267 (57%) patients had only worrisome features and 200 (43%) had at least 1 high-risk feature. UDD was present in 164 (35%) patients, of whom 118 (73%) had HGD/IC. On multivariable analysis, UDD increased the odds of HGD/IC by 2.8-fold, even while controlling for Fukuoka risk factors (95% CI: 1.8–4.4, P<0.001). Prevalence of HGD/IC in all patients with UDD was 73%, compared with 74% in patients with high-risk stigmata and 73% in patients with main duct IPMNs. In the secondary analysis, UDD increased the odds of HGD/IC by 3.2-fold in patients with dorsal BD-IPMNs (95% CI: 1.3–7.7, P=0.010).

Conclusions:
UDD confers additional risk for HGD/IC unaccounted for by current Fukuoka criteria. Further research can extend this study to Fukuoka-negative patients, including unresected patients.
Normothermic Regional Perfusion Can Improve Both Utilization and Outcomes in DCD Liver, Kidney, and Pancreas Transplantation
Authors: Bekki Yuki , Croome Kristopher P. , Myers Bryan , Sasaki Kazunari , Tomiyama Koji 
Published: February 2023

Background.
Normothermic regional perfusion (NRP) has gained widespread adoption in multiple European countries. The aim of this study was to examine the influence of thoracoabdominal-NRP (TA-NRP) on the utilization and outcomes of liver, kidney, and pancreas transplantation in the United States.

Methods.
Using the US national registry data between 2020 and 2021, donation after circulatory death (DCD) donors were separated into 2 groups: DCD with TA-NRP and without TA-NRP. There were 5234 DCD donors; among them 34 donors were with TA-NRP. After 1:4 propensity score matching, the utilization rates were compared between DCD with and without TA-NRP.

Results.
Although the utilization rates of kidney and pancreas were comparable (P = 0.71 and P = 0.06, 94.1% versus 95.6% and 8.8% versus 2.2%, respectively), that of liver in DCD with TA-NRP was significantly higher (P < 0.001; 70.6% versus 39.0%). Among 24 liver transplantations, 62 kidney transplantations, and 3 pancreas transplantations from DCD with TA-NRP, there were 2 liver grafts and 1 kidney graft that failed within 1 y after transplantation.

Conclusions.
TA-NRP in the United States significantly increased the utilization rate of abdominal organs from DCD donors with comparable outcomes after transplantation. Increasing use of NRP may expand the donor pool without compromising transplant outcomes.
Mechanisms of collective learning: how can animal groups improve collective performance when repeating a task?
Authors: Collet Julien , Morford Joe , Lewin Patrick , Bonnet-Lebrun Anne-Sophie , Sasaki Takao , Biro Dora 
Published: February 2023

Learning is ubiquitous in animals: individuals can use their experience to fine-tune behaviour and thus to better adapt to the environment during their lifetime. Observations have accumulated that, at the collective level, groups can also use their experience to improve collective performance. Yet, despite apparent simplicity, the links between individual learning capacities and a collective's performance can be extremely complex. Here we propose a centralized and broadly applicable framework to begin classifying this complexity. Focusing principally on groups with stable composition, we first identify three distinct ways through which groups can improve their collective performance when repeating a task: each member learning to better solve the task on its own, members learning about each other to better respond to one another and members learning to improve their complementarity. We show through selected empirical examples, simulations and theoretical treatments that these three categories identify distinct mechanisms with distinct consequences and predictions. These mechanisms extend well beyond current social learning and collective decision-making theories in explaining collective learning. Finally, our approach, definitions and categories help generate new empirical and theoretical research avenues, including charting the expected distribution of collective learning capacities across taxa and its links to social stability and evolution.
This article is part of a discussion meeting issue ‘Collective behaviour through time’.
Ageing in a collective: the impact of ageing individuals on social network structure
Authors: Siracusa Erin R. , Pereira André S. , Brask Josefine Bohr , Negron-Del Valle Josué E. , Phillips Daniel ,   Cayo Biobank Research Unit, Platt Michael L. , Higham James P. , Snyder-Mackler Noah , Brent Lauren J. N. 
Published: February 2023

Ageing affects many phenotypic traits, but its consequences for social behaviour have only recently become apparent. Social networks emerge from associations between individuals. The changes in sociality that occur as individuals get older are thus likely to impact network structure, yet this remains unstudied. Here we use empirical data from free-ranging rhesus macaques and an agent-based model to test how age-based changes in social behaviour feed up to influence: (i) an individual's level of indirect connectedness in their network and (ii) overall patterns of network structure. Our empirical analyses revealed that female macaques became less indirectly connected as they aged for some, but not for all network measures examined. This suggests that indirect connectivity is affected by ageing, and that ageing animals can remain well integrated in some social contexts. Surprisingly, we did not find evidence for a relationship between age distribution and the structure of female macaque networks. We used an agent-based model to gain further understanding of the link between age-based differences in sociality and global network structure, and under which circumstances global effects may be detectable. Overall, our results suggest a potentially important and underappreciated role of age in the structure and function of animal collectives, which warrants further investigation.
This article is part of a discussion meeting issue ‘Collective behaviour through time’.
The evolution of intergroup cooperation
Authors: Rodrigues António M. M. , Barker Jessica L. , Robinson Elva J. H. 
Published: February 2023

Sociality is widespread among animals, and involves complex relationships within and between social groups. While intragroup interactions are often cooperative, intergroup interactions typically involve conflict, or at best tolerance. Active cooperation between members of distinct, separate groups occurs very rarely, predominantly in some primate and ant species. Here, we ask why intergroup cooperation is so rare, and what conditions favour its evolution. We present a model incorporating intra- and intergroup relationships and local and long-distance dispersal. We show that dispersal modes play a pivotal role in the evolution of intergroup interactions. Both long-distance and local dispersal processes drive population social structure, and the costs and benefits of intergroup conflict, tolerance and cooperation. Overall, the evolution of multi-group interaction patterns, including both intergroup aggression and intergroup tolerance, or even altruism, is more likely with mostly localized dispersal. However, the evolution of these intergroup relationships may have significant ecological impacts, and this feedback may alter the ecological conditions that favour its own evolution. These results show that the evolution of intergroup cooperation is favoured by a specific set of conditions, and may not be evolutionarily stable. We discuss how our results relate to empirical evidence of intergroup cooperation in ants and primates.
This article is part of a discussion meeting issue ‘Collective behaviour through time’.