bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turbulence in Indian aviation financing sector: time to understand and implement the Cape Town regime in the true spirit
Authors: Bhat B. Sandeepa 
Published: July 2024

Abstract
India, being a vast country with middle-income population, requires speedy and economic means of transportation for connecting its different parts. With rail and road transportation not having immense success in providing speedy means of transportation, aviation connectivity is of prime importance to India. Unfortunately, the Indian aviation sector is having a disastrous run over the years with several big players ending up in bankruptcy. Added to this, several Indian laws stand as impediments to enforcing the rights of financiers in the aviation sector. Accordingly, the financiers are not willing to take the risk of investing in the Indian aviation sector. This issue has been continuing even after India has become a party to the Cape Town regime relating to aviation financing in 2008. The failure to implement the Cape Town regime is the chief reason for continued turbulence in Indian aviation financing. Hence, a probe into the Cape Town regime relating to aviation financing with a view to implement it in the true spirit attains great significance in India.
Balanced Business Decision-making for Clinical Practices: Fulfilling “Mission” and “Margin”
Authors: Chandawarkar Rajiv , Nadkarni Prakash 
Published: July 2024

Summary:
Clinical practices, both private and academic, need to be profitable to sustain themselves and grow. To manage them and drive profits, one needs leadership that has a well-rounded understanding of multiple facets. When business decisions are based on financial data alone, they meet the goal of profit margin but alienate clinicians; when made using clinical data alone, they fulfill the clinical mission but ignore the bottom line. Here, we explain the benefits of a sound business-minded leadership that integrates the nuances of financial data, the cadence of clinical practices, and the value of resources, and makes meaningful business decisions. These decisions create a strong bond between physicians and their administrative leaders, aligning their “mission” (provide better care), and their “margin” (profitability and growth). We explain critical aspects of each source of information and how to use them together to make business decisions. Recognizing that clinicians may not have access to methods of financial analysis, we also supply a prepopulated Excel spreadsheet that has all equations baked in, so that it can be readily used, filling in their own data to generate financial ratios. This work explains how sound decisions can be made using financial metrics, clinical data (here, plastic surgery), and resource utilization, to identify areas that can be improved and take steps to achieve results.
Reduction of Z alpha-1 antitrypsin polymers in human iPSC-hepatocytes and mice by LRRK2 inhibitors
Authors: Kent Deniz , Ng Soon Seng , Syanda Adam M. , Khoshkenar Payam , Ronzoni Riccardo , Li Chao Zheng , Zieger Marina , Greer Cindy , Hatch Stephanie , Segal Joe , Blackford Samuel J.I. , Im Yu Ri , Chowdary Vivek , Ismaili Taylor , Danovi Davide , Lewis Patrick A. , Irving James A. , Sahdeo Sunil , Lomas David A. , Ebner Daniel , Mueller Christian , Rashid S. Tamir 
Published: July 2024

Background:
Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by the inheritance of the serpin family A member 1 “Z” genetic variant driving alpha-1 antitrypsin (AAT) protein misfolding in hepatocytes. There are no approved medicines for this disease.

Methods:
We conducted a high-throughput image-based small molecule screen using patient-derived induced pluripotent stem cell-hepatocytes (iPSC-hepatocytes). Identified targets were validated in vitro using 3 independent patient iPSC lines. The effects of the identified target, leucine-rich repeat kinase 2 (LRRK2), were further evaluated in an animal model of A1ATD through histology and immunohistochemistry and in an autophagy-reporter line. Autophagy induction was assessed through immunoblot and immunofluorescence analyses.

Results:
Small-molecule screen performed in iPSC-hepatocytes identified LRRK2 as a potentially new therapeutic target. Of the commercially available LRRK2 inhibitors tested, we identified CZC-25146, a candidate with favorable pharmacokinetic properties, as capable of reducing polymer load, increasing normal AAT secretion, and reducing inflammatory cytokines in both cells and PiZ mice. Mechanistically, this effect was achieved through the induction of autophagy.

Conclusions:
Our findings support the use of CZC-25146 and leucine-rich repeat kinase-2 inhibitors in hepatic proteinopathy research and their further investigation as novel therapeutic candidates for A1ATD.
Amplifying Chinese physicians’ emphasis on patients’ psychological states beyond urologic diagnoses with ChatGPT – a multicenter cross-sectional study
Authors: Peng Lei , Liang Rui , Zhao Anguo , Sun Ruonan , Yi Fulin , Zhong Jianye , Li Rongkang , Zhu Shimao , Zhang Shaohua , Wu Song 
Published: July 2024

Background:
Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies of urology, ChatGPT offers a novel possibility to aid in clinical decision-making. This study aimed to investigate the decision-making ability of LLMs in solving complex urology-related problems and assess their effectiveness in providing psychological support to patients with urological disorders.

Materials and methods:
This study evaluated the clinical and psychological support capabilities of ChatGPT 3.5 and 4.0 in the field of urology. A total of 69 clinical and 30 psychological questions were posed to the AI models, and both urologists and psychologists evaluated their response. As a control, clinicians from Chinese medical institutions responded to closed-book conditions. Statistical analyses were conducted separately for each subgroup.

Results:
In multiple-choice tests covering diverse urological topics, ChatGPT 4.0 was performed comparably to the physician group, with no significant overall score difference. Subgroup analyses revealed variable performance based on disease type and physician experience, with ChatGPT 4.0 generally outperforming ChatGPT 3.5 and exhibiting competitive results against physicians. When assessing the psychological support capabilities of AI, it is evident that ChatGPT 4.0 outperforms ChatGPT 3.5 across all urology-related psychological problems.

Conclusions:
The performance of LLMs in dealing with standardized clinical problems and providing psychological support has certain advantages over clinicians. AI stands out as a promising tool for potential clinical aid.
Experiences of Black Women With Pelvic Floor Disorders—A Qualitative Analysis Study
Authors: Chyu Jennifer , Alimi Oriyomi , Popat Shreeya , Smith-Mathus Gjanje , Lee Una J. 
Published: July 2024

Importance
Disparities research in Black women with pelvic floor disorders (PFDs) has primarily focused on epidemiology or surgical outcomes, but little is known about the patient perspective on seeking PFD care.

Objective
To provide quality and equitable care to Black women with PFDs, we conducted a qualitative study to hear their perspectives and lived health care experiences.

Study Design
Black women seeking care for PFDs at a tertiary care institution were invited to participate in qualitative interviews. Open-ended questions explored participants’ knowledge, attitudes, and health care experiences. Interviews were transcribed verbatim and coded line-by-line. Inductive content analysis was performed to identify key themes, and consensus was achieved among the research team.

Results
Eight Black women aged 21–83 years consented to participate. Patients noted a stigma surrounding PFDs, both among health care professionals and their community. They noted several barriers to care: financial, logistical, and racial bias. They cited difficulties in patient–health care professional communication, including not feeling heard or treated as an individual. They preferred gender and racial concordance with their physicians. These women expressed both a desire for more knowledge and to share this knowledge and advocate for other women.

Conclusions
Black women expressed distinct obstacles in their PFD health care. They reported not feeling heard or treated as a unique individual. The themes derived from this study identify complex patient-centered needs that can serve as the basis for future quality improvement work and/or hypothesis-driven research. By grounding health disparities research in patient perspectives, we can improve the health care experiences of Black women.
Measurement of Physical Activity Using Fitness Trackers Before and After Midurethral Sling
Authors: Cope Zebulun S. , Stewart J Ryan , Gupta Ankita , Hobson Deslyn T.G. , Warehime Jenna , Feroz Rehan , Scheidel Sarah , Meriwether Kate V. , Lenger Stacy M. , Gaskins Jeremy T. , Sumy Sharmin , Francis Sean 
Published: July 2024

Importance
Urinary incontinence can be a barrier to performing physical activities for many women. A midurethral sling (MUS) has shown symptom improvement for women experiencing stress urinary incontinence (SUI), suggesting the hypothesis that physical activity rates should increase after treatment.

Objective
The aim of this study was to determine the change in objectively measured physical activity levels in women following placement of MUS for SUI.

Study Design
In this prospective cohort study, patients undergoing MUS placement, with or without concomitant pelvic reconstructive surgery, were provided a commercial activity tracker. Physical activity was tracked for at least 1 week preoperatively and up to 6 months postoperatively. Participants were required to wear the tracker for at least 2 weeks in the postoperative period. The primary outcome, mean caloric daily expenditure (MCDE), was compared preoperatively and postoperatively.

Results
Seventy-two patients met criteria for data inclusion. The device was worn for a mean of 18.4 ± 12.1 days preoperatively and 91.7 ± 53.3 days postoperatively. Mean participant age was 51.9 ± 9.4 years. The MCDE was significantly higher postoperatively (preoperatively: 1,673 kcal/d vs postoperatively: 2,018 kcal/d; P < 0.01). There were no significant differences in postoperative MCDE in participants who had only MUS as the primary procedure versus participants who also had a concomitant procedure (2,020 ± 216 kcal/d vs 2,015 ± 431 kcal/d; P = 0.95). Of participants with class II/III obesity, 45% had at least a 500 kcal/d increase postoperatively.

Conclusions
Treatment of SUI with MUS is associated with a significantly greater caloric expenditure in the postoperative period.
Acarbose ameliorates Western diet-induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer’s disease
Authors: Sonsalla Michelle M. , Babygirija Reji , Johnson Madeline , Cai Samuel , Cole Mari , Yeh Chung-Yang , Grunow Isaac , Liu Yang , Vertein Diana , Calubag Mariah F. , Trautman Michaela E. , Green Cara L. , Rigby Michael J. , Puglielli Luigi , Lamming Dudley W. 
Published: July 2024

AbstractAge is the greatest risk factor for Alzheimer’s disease (AD) as well as for other disorders that increase the risk of AD such as diabetes and obesity. There is growing interest in determining if interventions that promote metabolic health can prevent or delay AD. Acarbose is an anti-diabetic drug that not only improves glucose homeostasis, but also extends the lifespan of wild-type mice. Here, we test the hypothesis that acarbose will not only preserve metabolic health, but also slow or prevent AD pathology and cognitive deficits in 3xTg mice, a model of AD, fed either a Control diet or a high-fat, high-sucrose Western diet (WD). We find that acarbose decreases the body weight and adiposity of WD-fed 3xTg mice, increasing energy expenditure while also stimulating food consumption, and improves glycemic control. Both male and female WD-fed 3xTg mice have worsened cognitive deficits than Control-fed mice, and these deficits are ameliorated by acarbose treatment. Molecular and histological analysis of tau and amyloid pathology identified sex-specific effects of acarbose which are uncoupled from the dramatic improvements in cognition, suggesting that the benefits of acarbose on AD are largely driven by improved metabolic health. In conclusion, our results suggest that acarbose may be a promising intervention to prevent, delay, or even treat AD, especially in individuals consuming a Western diet.
Large-Scale Comparative Transcriptomic Analysis of CHO Cell Functional Adaptation to Recombinant Monoclonal Antibody Production
Authors: Alexandru-Crivac Cristina N. , Cartwright Joseph F. , Taylor Ryan , Sweeney Bernadette M. , Feary Marc , Chathoth Keerthi T. , Fabian Daniel K. , Allsopp Harry , Brown Adam J. , James David C. 
Published: July 2024

AbstractTo comparatively evaluate cellular constraints on recombinant monoclonal antibody (mAb) production by Chinese Hamster Ovary (CHO) cells, we analysed the transcriptomes of 24 clonally derived CHO cell lines engineered with PiggyBac transposon technology to stably produce four recombinant monoclonal antibodies (mAbs) at varying specific production rates. Fed-batch cultures were sampled at exponential (day 5) and stationary (day 10) phases of culture for analysis by RNA-Seq. Recombinant mRNAs accounted for a large proportion of total mRNA across all clones, and efficient use of heavy chain (HC) mRNA to synthesise recombinant mAb (qP per HC mRNA) varied significantly with respect to both mAb product and cell line. Comparative bioinformatic analyses of CHO transcriptomes focussed on mAb specific production rate and utilised both data-driven and hypothesis-led approaches, specifically (i) production or non-production of recombinant mAb, (ii) changes in the abundance of functional groups of mRNAs abundance with mAb specific production rate and (iii) comparative analysis of informatically-mined gene subsets associated with cellular functions hypothesised to impact recombinant mAb synthesis and secretion. These analyses revealed widespread constitutive and adaptive changes in mRNA abundance associated with mAb production across a variety of cellular functions. Typically, most mechanistically consistent changes in mRNA abundance co-varying with mAb production were evident at the stationary phase sample point. These data revealed both recombinant mAb-specific limitations on cellular synthetic capacity and a generic adaptive strategy used by CHO cells to support high-level mAb production. The latter was achieved by directed and permissive regulation of endoplasmic reticulum and other processes to accommodate increased synthetic flux.
Optimizing Genetic Testing Strategy for Suspected Attenuated Adenomatous Polyposis: Effective Solutions in Public Health Systems
Authors: García-Simón Natalia , Valentín Fátima , Royuela Ana , Hidalgo-Calero Beatriz , Blázquez-Martín Ricardo , de-Miguel-Reyes Montserrat , Sánchez-Zapardiel José M , Adán-Merino Luisa , Rodríguez-Festa Alejandro , Gallego-Gil Patricia , Mediavilla-Medel Pilar , Quiñonero-Moreno Laura , Gutiérrez Lourdes , Herreros-de-Tejada Alberto , Sánchez Antonio , Provencio Mariano , Romero Atocha 
Published: July 2024

ABSTRACTBACKGROUNDAttenuated familial adenomatous polyposis (AFAP) and MUTYH-associated polyposis (MAP) represent key hereditary attenuated adenomatous polyposis syndromes, withAPCandMUTYHbeing the associated genes. While guidelines recommend genetic testing based on polyp count for diagnosing these syndromes, age is often overlooked despite its influence on polyp prevalence.AIMTo enhance genetic testing strategies for suspected attenuated adenomatous polyposis by combining polyp count and age in a probability calculator.METHODSRetrospective study of adult patients referred to NGS genetic testing for suspected attenuated adenomatous polyposis (accumulated history of <100 adenomas) (discovery cohort, N=138). Data collected included age, adenoma count at the time of genetic testing, and test results. Multivariable logistic regression model was developed to link a positive genetic test result with age and adenoma count. The model was externally validated with populations from two tertiary hospitals in our region (validation cohort, N=259).RESULTSIn the discovery cohort, 13 (9.4%) patients tested positive for pathogenic mutations. Positive cases were younger (odds ratio (OR): 0.91, 95% confidence interval (95%IC): 0.86-0.96) and developed more adenomas (OR: 1.08, 95%IC: 1.04-1.13) compared to negative cases. The logistic regression model combining age and polyp count demonstrated an AUC of 0.92. Using a cutoff probability of 3.5%, the model achieved 100% sensitivity and 58% specificity in identifying positive cases. In the external validation, the model accurately predicted 14 out of 16 positive cases (88%). The remaining two positive cases were a patient with anAXIN2mutation in heterozygosis, and a patient with aNTHL1mutation in homozygosis. Performance evaluation of both hospitals yielded AUC values of 0.77 and 0.90.CONCLUSIONSOlder individuals, particularly those with few polyps, may have diminished chances of detecting hereditary syndromes. Incorporating age as a criterion for genetic testing referral has the potential to refine patient selection and improve cost-effectiveness.Core tipThis retrospective muli-center observational study aims to investigate the weight of age and polyp count on patients diagnosed with hereditary attenuated adenomatous polyposis syndrome compared to those with sporadic polyposis. Base on this, a probability calculator has been developed to enhance the efficiency and cost-effectiveness of genetic testing protocols for attenuated adenomatous polyposis syndromes within public health systems.
CARDIOGENIC SHOCK MORTALITY ACCORDING TO AETIOLOGY IN A MEDITERRANEAN COHORT: RESULTS FROM THE SHOCK-CAT STUDY
Authors: García-García Cosme , López-Sobrino Teresa , Sanz-Girgas Esther , Cueto Maria Ruiz , Aboal Jaime , Pastor Pablo , Buera Irene , Sionis Alessandro , Andrea Rut- , Rodríguez-López Judit , Sánchez-Salado JC , Querol Carlos Tomas , Bañeras Jordi , Sole Albert Ariza , Lupón Josep , Bayés-Genís Antoni , Rueda Ferran 
Published: July 2024

ABSTRACTBackground and objectivesMortality in cardiogenic shock (CS) remains elevated, with the potential for CS causes to impact prognosis and risk stratification. The aim was to investigate in-hospital prognosis and mortality in CS patients according to aetiology. We also assessed the prognostic accuracy of CardShock and IABP-SHOCK II scores.MethodsShock-CAT study was a multicentre, prospective, observational study conducted from December 2018-November 2019 in eight University hospitals in Catalonia, including non-selected consecutive CS patients. Data on clinical presentation, management, including mechanical circulatory support (MCS) were analysed comparing acute myocardial infarction (AMI) related CS and non-AMI-CS. The accuracy of CardShock and IABP-SHOCK II scores to assess 90-days mortality risk were also compared.ResultsA total of 382 CS patients were included, age 65.3 (SD 13.9) years, 75.1% men. Patients were classified as AMI-CS (n=232, 60.7%) and non-AMI-CS (n=150, 39.3%). In the AMI-CS group, 77.6% were STEMI. Main aetiologies for non-AMI-CS were heart failure (36.2%), arrhythmias (22.1%) and valve disease (8.0%). AMI-CS patients required more MCS than non-AMI-CS (43.1% vs 16.7%, p<0.001). In-hospital mortality was higher in AMI-CS (37.1 vs 26.7%, p=0.035), with a two-fold increased risk after multivariate adjustment (OR 2.24, p=0.019). The IABP-SHOCK II had superior discrimination for predicting 90-days mortality when compared with CardShock in AMI-CS patients (AUC 0.74 vs 0.66, p=0.047) although both scores performed similarly in non-AMI-CS (AUC 0.64 vs 0.62, p=0.693).ConclusionsIn our cohort, AMI-CS mortality was increased by two-fold when compared to non- AMI-CS. IABP-SHOCK II score provides better 90-days mortality risk prediction than CardShock score in AMI-CS, but both scores performed similar in non-AMI-CS patients.
High feasibility of salivary therapeutic drug monitoring in linezolid, but less in tedizolid: A single-dose study in healthy subjects
Authors: Kawasuji Hitoshi , Tsuji Yasuhiro , Miyaki Keiko , Aoyama Takahiko , Kurosaki Fumihiro , Ezaki Masayoshi , Koshiyama Yuki , Takegoshi Yusuke , Kaneda Makito , Murai Yushi , Kimoto Kou , Nagaoka Kentaro , Yamamoto Yoshihiro 
Published: July 2024

ABSTRACTBackgroundSalivary therapeutic drug monitoring (TDM) offers the potential to reduce the risks, burden, time, and costs of blood-based TDM, but its feasibility in oxazolidinone antibiotics and the influence of food intake remain unknown.MethodsA total of 12 healthy volunteers participated in this study. Linezolid and tedizolid were intravenously administered to 6 participants each. Saliva samples were taken at 15 time points and peripheral venous blood samples were also taken at 12 time points simultaneously with saliva. Total and unbound serum and saliva concentrations of linezolid and tedizolid were measured using high-performance liquid chromatography.ResultsIndividual concentration–time curves in saliva versus serum (total and unbound) were similar in linezolid, but different in tedizolid. Saliva concentrations were significantly correlated with total and unbound serum concentrations in both agents. However, concentrations in each case and area under the concentration–time curve from 0 to 10 h (AUC0–10) in saliva were correlated with those in total or unbound serum for linezolid, but not for tedizolid. The mean saliva-to-serum (total and unbound) concentration and AUC0–10ratios were 0.90 and 0.90 in total and 1.09 and 0.99 in unbound. Food intake did not influence these correlations in linezolid.ConclusionsThe analysis of linezolid in saliva is applicable for TDM as a promising alternative to conventional serum sampling without correlation factors, but application of tedizolid is less feasible. Easy sampling using a noninvasive technique may facilitate TDM even in underdeveloped countries with limited resources and specific patient categories.