bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of clinical newborn metabolic screening in a high-volume maternity center in Nepal
Authors: Khan Janine Y. , Subedi Kalpana U. , Karmacharya Shailendra B. , Paudel Prajwal , Manandhar Dharma S. , Hennessy Garza Rose , Dookeran Keith A. , Manandhar Sunil R. 
Published: February 2024

Abstract
Background
Strategic action plans around newborn health evaluation are needed, to address the high neonatal mortality rate in Nepal. Surveillance systems, like Newborn Metabolic Screening (NBS), could reveal unrecognized drivers of neonatal death. NBS is not routinely performed in Nepal. Our objective was to determine the feasibility of establishing NBS, and its acceptability among healthcare providers and parents, in Nepal.

Methods
This prospective cohort study was conducted between November 2021 and May 2022 in term/late preterm infants born at Paropakar Maternity Hospital, Kathmandu, screening for 6 disorders that can be confirmed and managed locally. Staff were trained on dried-blood spot collection and transport protocols, performance metrics were established, and assays were performed at an accredited laboratory in Bangalore, India. Surveys were developed to determine acceptability among health-care providers and parents.

Results
Of 835 parents approached for the study, 825 (98.8%) consented. Parental surveys showed that 92% considered “no cost” option most important in choosing to participate in the study. Samples were transported to laboratories in Kathmandu and Bangalore in 36 ± 24 h, and 4.75 ± 1 days, which exceeded expected metrics of 24 and 48 h, respectively. Results were communicated to parents by 9.5 ± 2 days, which was within the expected metric window of 14 days. Abnormalities were reported in 13 infants and included 5 hemoglobinopathy traits (4 Hb E and 1 Hb D), 3 congenital hypothyroidism, 2 glucose-6-phosphate dehydrogenase deficiency, 1 congenital adrenal hyperplasia, 1 elevated acylcarnitine, and 1 biotinidase deficiency. Healthcare providers surveyed (n = 116) showed that 67% reported a moderate understanding of NBS; all indicated that screening would be beneficial. Most cited early diagnosis and treatment, as well as, providing risk to future pregnancies as significant benefits. 90% thought screening should be routinely performed.

Conclusions
We demonstrate that it is feasible to introduce NBS in Nepal. Transport metrics were longer than expected due to COVID pandemic travel restrictions; however, it was possible to deliver results to families within 2 weeks of birth. Parents overwhelmingly considered “no cost” option as the most important in choosing to screen. A government-sponsored program will be a key factor in establishing NBS in Nepal.
Long-Term Follow-Up of the Anthracyclines in Early Breast Cancer Trials (USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 [NRG Oncology])
Authors: Geyer Charles E. , Blum Joanne L. , Yothers Greg , Asmar Lina , Flynn Patrick J. , Robert Nicholas J. , Hopkins Judith O. , O'Shaughnessy Joyce A. , Rastogi Priya , Puhalla Shannon L. , Hilton Christie J. , Dang Chau T. , Gómez Henry Leonidas , Vukelja Svetislava J. , Lyss Alan P. , Paul Devchand , Brufsky Adam M. , Colangelo Linda H. , Swain Sandra M. , Mamounas Eleftherios P. , Wolmark Norman 
Published: February 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The primary joint efficacy analysis of the Anthracyclines in Early Breast Cancer (ABC) trials reported in 2017 failed to demonstrate nonanthracycline adjuvant therapy was noninferior to anthracycline-based regimens in high-risk, early breast cancer. Full analyses of the studies had proceeded when the prespecified futility boundary was crossed at a planned futility analysis for the ability to demonstrate noninferiority of a nonanthracycline regimen with continued follow-up. These results were presented with 3.3 years of median follow-up. This manuscript reports results of the final analyses of the study efficacy end points conducted with 6.9 years of median follow-up. Long-term analysis of invasive disease-free survival (IDFS), the primary end point of the ABC trials, remains consistent with the original results, as noninferiority of the nonanthracycline regimens could not be declared on the basis of the original criteria. The secondary end point of recurrence-free interval, which excluded deaths not due to breast cancer as events, favored anthracycline-based regimens, and tests for heterogeneity were significant for hormone receptor status ( P = .02) favoring anthracycline regimens for the hormone receptor–negative cohorts. There was no difference in overall survival, and review of the type of IDFS events in the groups suggested reductions in cancer recurrences achieved with anthracycline regimens were offset by late leukemias and deaths unrelated to breast cancer.
Testosterone Treatment, Weight Loss, and Health-related Quality of Life and Psychosocial Function in Men: A 2-year Randomized Controlled Trial
Authors: Grossmann Mathis , Robledo Kristy P , Daniel Mark , Handelsman David J , Inder Warrick J , Stuckey Bronwyn G A , Yeap Bu B , Ng Tang Fui Mark , Bracken Karen , Allan Carolyn A , Jesudason David , Zajac Jeffrey D , Wittert Gary A 
Published: February 2024

Abstract

Objective
To determine the effect of testosterone vs placebo treatment on health-related quality of life (HR-QOL) and psychosocial function in men without pathologic hypogonadism in the context of a lifestyle intervention.

Design, Setting, Participants
Secondary analysis of a 2-year randomized controlled testosterone therapy trial for prevention or reversal of newly diagnosed type 2 diabetes, enrolling men ≥ 50 years at high risk for type 2 diabetes from 6 Australian centers.

Interventions
Injectable testosterone undecanoate or matching placebo on the background of a community-based lifestyle program.

Main Outcomes
Self-reported measures of HR-QOL/psychosocial function.

Results
Of 1007 participants randomized into the Testosterone for Type 2 Diabetes Mellitus (T4DM) trial, 648 (64%) had complete data available for all HR-QOL/psychosocial function assessments at baseline and 2 years. Over 24 months, while most measures were not different between treatment arms, testosterone treatment, compared with placebo, improved subjective social status and sense of coherence. Baseline HR-QOL/psychosocial function measures did not predict the effect of testosterone treatment on glycemic outcomes, primary endpoints of T4DM. Irrespective of treatment allocation, larger decreases in body weight were associated with improved mental quality of life, mastery, and subjective social status. Men with better baseline physical function, greater sense of coherence, and fewer depressive symptoms experienced greater associated decreases in body weight, with similar effects on waist circumference.

Conclusion
In this diabetes prevention trial, weight loss induced by a lifestyle intervention improved HR-QOL and psychosocial function in more domains than testosterone treatment. The magnitude of weight and waist circumference reduction were predicted by baseline physical function, depressive symptomology, and sense of coherence.
Thoracic Epidural Analgesia Is Not Associated With Improved Survival After Pancreatic Surgery: Long-Term Follow-Up of the Randomized Controlled PAKMAN Trial
Authors: Klotz Rosa , Ahmed Azaz , Tremmel Anja , Büsch Christopher , Tenckhoff Solveig , Doerr-Harim Colette , Lock Johan F. , Brede Elmar-Marc , Köninger Jörg , Schiff Jan-Henrik , Wittel Uwe A. , Hötzel Alexander , Keck Tobias , Nau Carla , Amati Anca-Laura , Koch Christian , Diener Markus K. , Weigand Markus A. , Büchler Markus W. , Knebel Phillip , Larmann Jan 
Published: February 2024

BACKGROUND:
Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are common forms of analgesia after pancreatic surgery. Current guidelines recommend EDA over PCIA, and evidence suggests that EDA may improve long-term survival after surgery, especially in cancer patients. The aim of this study was to determine whether perioperative EDA is associated with an improved patient prognosis compared to PCIA in pancreatic surgery.

METHODS:
The PAKMAN trial was an adaptive, pragmatic, international, multicenter, randomized controlled superiority trial conducted from June 2015 to October 2017. Three to five years after index surgery a long-term follow-up was performed from October 2020 to April 2021.

RESULTS:
For long-term follow-up of survival, 109 patients with EDA were compared to 111 patients with PCIA after partial pancreatoduodenectomy (PD). Long-term follow-up of quality of life (QoL) and pain assessment was available for 40 patients with EDA and 45 patients with PCIA (questionnaire response rate: 94%). Survival analysis revealed that EDA, when compared to PCIA, was not associated with improved overall survival (OS, HR, 1.176, 95% HR-CI, 0.809–1.710, P = .397, n = 220). Likewise, recurrence-free survival did not differ between groups (HR, 1.116, 95% HR-CI, 0.817–1.664, P = .397, n = 220). OS subgroup analysis including only patients with malignancies showed no significant difference between EDA and PCIA (HR, 1.369, 95% HR-CI, 0.932–2.011, P = .109, n = 179). Similar long-term effects on QoL and pain severity were observed in both groups (EDA: n = 40, PCIA: n = 45).

CONCLUSIONS:
Results from this long-term follow-up of the PAKMAN randomized controlled trial do not support favoring EDA over PCIA in pancreatic surgery. Until further evidence is available, EDA and PCIA should be considered similar regarding long-term survival.
Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study
Authors: Liu Sunny Yang , Kelly-Hedrick Margot , Komisarow Jordan , Hatfield Jordan , Ohnuma Tetsu , Treggiari Miriam M. , Colton Katharine , Arulraja Evangeline , Vavilala Monica S. , Laskowitz Daniel T. , Mathew Joseph P. , Hernandez Adrian , James Michael L. , Raghunathan Karthik , Krishnamoorthy Vijay 
Published: February 2024

BACKGROUND:
Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States.

METHODS:
We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes.

RESULTS:
The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47–0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09–1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01–1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73–1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78–1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93–1.03; P = .66).

CONCLUSIONS:
Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.
The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study
Authors: Shang Zixiang , Jiang Yu , Fang Panpan , Zhu Wenjie , Guo Jiaxin , Li Lili , Liang Yongjie , Zhang Sichen , Ma Shenglan , Mei Bin , Fan Yinguang , Xie Zhongcong , Shen Qiying , Liu Xuesheng 
Published: February 2024

BACKGROUND:
Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD.

METHODS:
This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1–7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power.

RESULTS:
A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4–8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6–60%; P = .021) of the association between diabetes and POD.

CONCLUSIONS:
This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.
Vertebral Bone Quality Score as a Predictor of Adjacent Segment Disease After Lumbar Interbody Fusion
Authors: Kuo Cathleen C. , Soliman Mohamed A. R. , Baig Rehman Ali , Aguirre Alexander O. , Ruggiero Nicco , Donnelly Brianna M. , Siddiqi Manhal , Khan Asham , Quiceno Esteban , Mullin Jeffrey P. , Pollina John 
Published: February 2024

BACKGROUND AND OBJECTIVE:
With lumbar spine fusion being one of the most commonly performed spinal surgeries, investigating common complications such as adjacent segment disease (ASD) is a high priority. To the authors' knowledge, there are no previous studies investigating the utility of the preoperative magnetic resonance imaging–based vertebral bone quality (VBQ) score in predicting radiographic and surgical ASD after lumbar spine fusion. We aimed to investigate the predictive factors for radiographic and surgical ASD, focusing on the predictive potential of the VBQ score.

METHODS:
A single-center retrospective analysis was conducted of all patients who underwent 1–3 level lumbar or lumbosacral interbody fusion for lumbar spine degenerative disease between 2014 and 2021 with a minimum 12 months of clinical and radiographic follow-up. Demographic data were collected, along with patient medical, and surgical data. Preoperative MRI was assessed in the included patients using the VBQ scoring system to identify whether radiographic ASD or surgical ASD could be predicted.

RESULTS:
A total of 417 patients were identified (mean age, 59.8 ± 12.4 years; women, 54.0%). Eighty-two (19.7%) patients developed radiographic ASD, and 58 (13.9%) developed surgical ASD. A higher VBQ score was a significant predictor of radiographic ASD in univariate analysis (2.4 ± 0.5 vs 3.3 ± 0.4; P < .001) and multivariate analysis (odds ratio, 1.601; 95% CI, 1.453-1.763; P < .001). For surgical ASD, a significantly higher VBQ score was seen in univariate analysis (2.3 ± 0.5 vs 3.3 ± 0.4; P < .001) and served as an independent risk factor in multivariate analysis (odds ratio, 1.509; 95% CI, 1.324-1.720; P < .001). We also identified preoperative disk bulge and preoperative existence of adjacent segment disk degeneration to be significant predictors of both radiographic and surgical ASD. Furthermore, 3-level fusion was also a significant predictor for surgical ASD.

CONCLUSION:
The VBQ scoring system might be a useful adjunct for predicting radiographic and surgical ASD.
The contribution of asymmetric cell division to phenotypic heterogeneity in cancer
Authors: Buss Julieti Huch , Begnini Karine Rech , Lenz Guido 
Published: February 2024

ABSTRACT
Cells have evolved intricate mechanisms for dividing their contents in the most symmetric way during mitosis. However, a small proportion of cell divisions results in asymmetric segregation of cellular components, which leads to differences in the characteristics of daughter cells. Although the classical function of asymmetric cell division (ACD) in the regulation of pluripotency is the generation of one differentiated daughter cell and one self-renewing stem cell, recent evidence suggests that ACD plays a role in other physiological processes. In cancer, tumor heterogeneity can result from the asymmetric segregation of genetic material and other cellular components, resulting in cell-to-cell differences in fitness and response to therapy. Defining the contribution of ACD in generating differences in key features relevant to cancer biology is crucial to advancing our understanding of the causes of tumor heterogeneity and developing strategies to mitigate or counteract it. In this Review, we delve into the occurrence of asymmetric mitosis in cancer cells and consider how ACD contributes to the variability of several phenotypes. By synthesizing the current literature, we explore the molecular mechanisms underlying ACD, the implications of phenotypic heterogeneity in cancer, and the complex interplay between these two phenomena.
Exact and Heuristic Solution Techniques for Mixed-Integer Quantile Minimization Problems
Authors: Cattaruzza Diego , Labbé Martine , Petris Matteo , Roland Marius , Schmidt Martin 
Published: February 2024

We consider mixed-integer linear quantile minimization problems that yield large-scale problems that are very hard to solve for real-world instances. We motivate the study of this problem class by two important real-world problems: a maintenance planning problem for electricity networks and a quantile-based variant of the classic portfolio optimization problem. For these problems, we develop valid inequalities and present an overlapping alternating direction method. Moreover, we discuss an adaptive scenario clustering method for which we prove that it terminates after a finite number of iterations with a global optimal solution. We study the computational impact of all presented techniques and finally show that their combination leads to an overall method that can solve the maintenance planning problem on large-scale real-world instances provided by the ROADEF/EURO challenge 2020 1 and that they also lead to significant improvements when solving a quantile-version of the classic portfolio optimization problem. History: Accepted by Andrea Lodi, Area Editor for Design & Analysis of Algorithms–Discrete. Funding: This work was supported by the Deutsche Forschungsgemeinschaft [CRC TRR 154], Fonds De La Recherche Scientifique [PDR T0098.18], and Bundesministerium für Bildung und Forschung. Supplemental Material: The online appendix is available at https://doi.org/10.1287/ijoc.2022.0105 .
Jam in the Tunnel: On Urban Freight Tunnels, Their Operational Scheduling, and Unused Transport Capacity
Authors: Boysen Nils , Briskorn Dirk , Rupp Johannes , Schwerdfeger Stefan 
Published: February 2024

Underground passageways for the transport of goods and people have fascinated mankind throughout the centuries. Recent initiatives in different parts of the world aim at rekindling the freight tunnel concept for urban logistics. According to this concept, freight is lifted into a tunnel, moved via electrically powered vehicles, rail cars, or maglev shuttles toward inner-city microhubs, and finally delivered with environmentally friendly vehicles to urban recipients. The main justification for this concept to outweigh the huge tunnel boring cost is a substantial reduction of road-based urban freight traffic. To warn about unfulfilled expectations, however, we show that the combination of time-critical goods, small inner-city hubs with restricted storage capacity, and the wrong booking procedure can hinder a loading of tunnel vehicles to capacity. To do so, we consider a polynomially solvable scheduling problem where due date-restricted shipments are to be assigned to tunnel vehicles and delivered to a given set of microhubs with limited storage capacity. Scarce hub capacities, tight due dates, and the wrong booking policy may not only lead to unused tunnel capacity but also to shipments that cannot be feasibly transported through the tunnel. If they are handed over to trucks as a fallback option, we show that a Braess-like paradox can occur: The time-critical, small-lot transports of the leftover shipments can produce even more surface traffic than trucking all shipments right from the start without the tunnel. Supplemental Material: The online appendices are available at https://doi.org/10.1287/serv.2023.0005 .