bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasticity of mitochondrial function safeguards phosphorylating respiration during in vitro simulation of rest‐phase hypothermia
Authors: García‐Díaz Carmen C. , Chamkha Imen , Elmér Eskil , Nord Andreas 
Published: March 2023

AbstractMany animals downregulate body temperature to save energy when resting (rest‐phase hypothermia). Small birds that winter at high latitudes have comparatively limited capacity for hypothermia and so pay large energy costs for thermoregulation during cold nights. Available evidence suggests this process is fueled by adenosine triphosphate (ATP)‐dependent mechanisms. Most ATP is produced by oxidative phosphorylation in the mitochondria, but mitochondrial respiration may be lower during hypothermia because of the temperature dependence of biological processes. This can create conflict between increased organismal ATP demand and a lower mitochondrial capacity to provide it. We studied this in blood cell mitochondria of wild great tits (Parus major) by simulating rest‐phase hypothermia via a 6°C reduction in assay temperature in vitro. The birds had spent the night preceding the experiment in thermoneutrality or in temperatures representing mild or very cold winter nights, but night temperatures never affected mitochondrial respiration. However, across temperature groups, endogenous respiration was 14% lower in hypothermia. This did not reflect general thermal suppression of mitochondrial function because phosphorylating respiration was unaffected by thermal state. Instead, hypothermia was associated with a threefold reduction of leak respiration, from 17% in normothermia to 4% in hypothermia. Thus, the coupling of total respiration to ATP production was 96% in hypothermia, compared to 83% in normothermia. Our study shows that the thermal insensitivity of phosphorylation combined with short‐term plasticity of leak respiration may safeguard ATP production when endogenous respiration is suppressed. This casts new light on the process by which small birds endure harsh winter cold and warrants future tests across tissues in vivo.
Predicting Deformity Correction of Growth Modulation in Late-onset Tibia Vara
Authors: Walker Janet L. , Dueber David M. , Powell Kenneth P. , Stephenson Lindsay P. , Scott Allison C. , Lerman Joel A. , Nossov Sarah B. , Franklin Corinna C. , Westberry David E. 
Published: March 2023

Background:
Growth modulation in late-onset tibia vara (LOTV) has been reported to yield variable results. We hypothesized that parameters of deformity severity, skeletal maturity, and body weight could predict the odds of a successful outcome.

Methods:
A retrospective review of tension band growth modulation for LOTV (onset ≥8 y) was performed at 7 centers. Tibial/overall limb deformity and hip/knee physeal maturity were assessed on preoperative anteroposterior standing lower-extremity digital radiographs. Tibial deformity change with first-time lateral tibial tension band plating (first LTTBP) was assessed by medial proximal tibia angle (MPTA). Effects of a growth modulation series (GMS) on overall limb alignment were assessed by mechanical tibiofemoral angle (mTFA) and included changes from implant removal, revision, reimplantation, subsequent growth, and femoral procedures during the study period. The successful outcome was defined as radiographic resolution of varus deformity or valgus overcorrection. Patient demographics, characteristics, maturity, deformity, and implant selections were assessed as outcome predictors using multiple logistic regression.

Results:
Fifty-four patients (76 limbs) had 84 LTTBP procedures and 29 femoral tension band procedures. For each 1-degree decrease in preoperative MPTA or 1-degree increase in preoperative mTFA the odds of their successful correction decreased by 26% in the first LTTBP and 6% by GMS, respectively, controlling for maturity. The change in odds of success for GMS assessed by mTFA was similar when controlling for weight. Closure of a proximal femoral physis decreased the odds of success for postoperative-MPTA by 91% with first LTTBP and for final-mTFA by 90% with GMS, controlling for preoperative deformity. Preoperative weight ≥100 kg decreased the odds of success for final-mTFA with GMS by 82%, controlling for preoperative mTFA. Age, sex, race/ethnicity, type of implant, and knee center peak value adjusted age (a method for bone age) were not predictive of outcome.

Conclusions:
Resolution of varus alignment in LOTV using first LTTBP and GMS, as quantified by MPTA and mTFA, respectively, is negatively impacted by deformity magnitude, hip physeal closure, and/or body weight ≥100 kg. The presented table, utilizing these variables, is helpful in the prediction of the outcome of the first LTTBP and GMS. Even if complete correction is not predicted, growth modulation may still be appropriate to reduce deformity in high-risk patients.

Level of Evidence:
Level III.
Subgroups of Idiopathic Clubfoot Can Predict Short-term Outcomes
Authors: Quinlan Rachal , Pacey Verity , Ilhan Emre , Gibbons Paul , Gray Kelly 
Published: March 2023

Background:
The Pirani scale is used for the assessment of Ponseti-managed clubfoot. Predicting outcomes using the total Pirani scale score has varied results, however, the prognostic value of midfoot and hindfoot components remains unknown. The purpose was to (1) determine the existence of subgroups of Ponseti-managed idiopathic clubfoot based on the trajectory of change in midfoot and hindfoot Pirani scale scores, (2) identify time points, at which subgroups can be distinguished, and (3) determine whether subgroups are associated with the number of casts required for correction and need for Achilles tenotomy.

Methods:
Medical records of 226 children with 335 idiopathic clubfeet, over a 12-year period, were reviewed. Group-based trajectory modeling of the Pirani scale midfoot score and hindfoot score identified subgroups of clubfoot that followed statistically distinct patterns of change during initial Ponseti management. Generalized estimating equations determined the time point, at which subgroups could be distinguished. Comparisons between groups were determined using the Kruskal-Wallis test for the number of casts required for correction and binary logistic regression analysis for the need for tenotomy.

Results:
Four subgroups were identified based on the rate of midfoot-hindfoot change: (1) fast-steady (61%), (2) steady-steady (19%), (3) fast-nil (7%), and (4) steady-nil (14%). The fast-steady subgroup can be distinguished at the removal of the second cast and all other subgroups can be distinguished at the removal of the fourth cast [H (3) = 228.76, P < 0.001]. There was a significant statistical, not clinical, difference in the total number of casts required for correction across the 4 subgroups [median number of casts 5 to 6 in all groups, H (3) = 43.82, P < 0.001]. Need for tenotomy was significantly less in the fast-steady (51%) subgroup compared with the steady-steady (80%) subgroup [H (1) = 16.23, P < 0.001]; tenotomy rates did not differ between the fast-nil (91%) and steady-nil (100%) subgroups [H (1) = 4.13, P = 0.04].

Conclusions:
Four distinct subgroups of idiopathic clubfoot were identified. Tenotomy rate differs between the subgroups highlighting the clinical benefit of subgrouping to predict outcomes in Ponseti-managed idiopathic clubfoot.

Level of Evidence:
Level II, prognostic.
Fibrin Glue is a Viable Alternative to Fat Graft for Interposition After Tarsal Coalition Resection
Authors: Swonger Ronald M. , Bernstein Jessica M. , Perez Olivia F. , Syros Alina , Horowitz Kevin S. , Schreiber Verena M. 
Published: March 2023

Background:
Tarsal coalition is one of the most common foot and ankle pathologies in children, yet there is no consensus regarding what to interpose after resection. Fibrin glue could be considered, but the literature comparing fibrin glue to other interposition types is sparse. The purpose of this study was to evaluate the effectiveness of fibrin glue for interposition compared with fat graft by analyzing the rate of coalition recurrence and wound complications. We hypothesized that fibrin glue would have similar rates of coalition recurrence and fewer wound complications compared with fat graft interposition.

Methods:
A retrospective cohort study was performed examining all patients who underwent a tarsal coalition resection at a free-standing children’s hospital in the United States from 2000 to 2021. Only patients undergoing isolated primary tarsal coalition resection with interposition of fibrin glue or fat graft were included. Wound complications were defined as any concern for an incision site that prompted the use of antibiotics. Comparative analyses were conducted using χ2 and Fisher exact test to examine relationships among interposition type, coalition recurrence, and wound complications.

Results:
One hundred twenty-two tarsal coalition resections met our inclusion criteria. Fibrin glue was used for interposition in 29 cases and fat graft was used in 93 cases. The difference in the coalition recurrence rate between fibrin glue and fat graft interposition was not statistically significant (6.9% vs. 4.3%, P=0.627). The difference in wound complication rate between fibrin glue and fat graft interposition was not statistically significant (3.4% vs 7.5%, P = 0.679).

Conclusion:
Fibrin glue interposition after tarsal coalition resection is a viable alternative to fat graft interposition. Fibrin glue has similar rates of coalition recurrence and wound complications when compared with fat grafts. Given our results and the lack of tissue harvesting required with fibrin glue, fibrin glue may be superior to fat grafts for interposition after tarsal coalition resection.

Level of Evidence:
Level III, a retrospective comparative study between treatment groups.
Current applications for magnetic resonance-guided focused ultrasound in the treatment of Parkinson's disease
Authors: Lu Haoxuan , Wang Xiaoyu , Lou Xin 
Published: March 2023

Abstract
Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel and minimally invasive technology. Since the US Food and Drug Administration approved unilateral ventral intermediate nucleus-MRgFUS for medication-refractory essential tremor in 2016, studies on new indications, such as Parkinson's disease (PD), psychiatric diseases, and brain tumors, have been on the rise, and MRgFUS has become a promising method to treat such neurological diseases. Currently, as the second most common degenerative disease, PD is a research hotspot in the field of MRgFUS. The actions of MRgFUS on the brain range from thermoablation, blood-brain barrier (BBB) opening, to neuromodulation. Intensity is a key determinant of ultrasound actions. Generally, high intensity can be used to precisely thermoablate brain targets, whereas low intensity can be used as molecular therapies to modulate neuronal activity and open the BBB in conjunction with injected microbubbles. Here, we aimed to summarize advances in the application of MRgFUS for the treatment of PD, with a focus on thermal ablation, BBB opening, and neuromodulation, in the hope of informing clinicians of current applications.
Low-dose aspirin in the prevention of pre-eclampsia in China: postpartum hemorrhage in subgroups of women according to their characteristics and potential bleeding risk
Authors: Chen Jiahui , Huai Jing , Lin Li , Li Boya , Zhu Yuchun , Yang Huixia 
Published: March 2023

Abstract

Background:
The APPEC study is a large-population randomized controlled trial in China evaluating the role of low-dose aspirin prophylactic treatment for pre-eclampsia. There was no statistically significant difference in postpartum hemorrhage (PPH) incidence between the aspirin and control groups. This study aimed to evaluate the potential bleeding risk of 100 mg aspirin in high-risk pregnant women and the difference in the incidence of PPH according to maternal characteristics.

Methods:
This is a secondary data analysis of the APPEC study. Platelet counts and coagulation test results were collected at five follow-up visits. Subgroups defined by maternal age (<35 years and ≥35 years), pre-pregnancy body mass index (pre-BMI, <28 kg/m2 and ≥28 kg/m2), parity, gestational age at enrollment, and medical history, including pre-eclampsia, chronic hypertension, and diabetes mellitus, were analyzed. Logistic regression analysis was used to determine the statistical significance of the difference in the incidence of PPH after aspirin administration in pregnant women in each subgroup. Adjustment using multiple logistic regression models followed these analyses. Binary logistic regression was used to determine the relationship between pre-BMI and PPH.

Results:
There was no significant difference between the aspirin and control groups in bleeding risk (3.4% [16/464] vs. 3.0% [13/434], T = 0.147, P = 0.701). No significant difference was found in the incidence of PPH in total (relative risk  = 1.220, 95% confidence interval [CI] = 0.720–2.067, P = 0.459; aspirin group vs. control group, 6.5% [30/464] vs. 5.3% [23/434], P = 0.459) or in subgroup analysis. A significant correlation between pre-BMI and PPH was found in the aspirin group, while in the control group there was no significant correlation (aspirin group, odds ratio [OR] = 1.086, 95% CI = 1.004–1.175, P = 0.040; control group, OR = 1.060, 95% CI = 0.968–1.161, P = 0.209).

Conclusions:
A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not increase the risk of potential bleeding and PPH regardless of the maternal characteristic. In the aspirin group, the positive correlation between BMI and PPH was significant.

Trial Registration:
ClinicalTrials.gov, NCT01979627.
Long-term outcomes of additional surgery versus non-gastrectomy treatment for early gastric cancer after non-curative endoscopic submucosal dissection: a meta-analysis
Authors: Li Sixuan , Tian Xueli , Wei Jingyao , Shi Yanyan , Zhang Hua , Huang Yonghui 
Published: March 2023

Abstract

Background:
Endoscopic resection is increasingly used in the treatment for early gastric cancer (EGC); however, about 15% of endoscopic submucosal dissection (ESD) cases report non-curative resection. The efficacy of different remedial interventions after non-curative ESD for EGC remains controversial. This meta-analysis aimed to compare the long-term outcomes of additional surgery and non-gastrectomy treatment for EGC patients who underwent non-curative ESD.

Methods:
All relevant studies published up to October 2021 were systematically searched in the PubMed, Web of Science, and Embase databases. The medical subject headings terms “early gastric cancer,” “gastrectomy,” “endoscopic submucosal dissection,” and their related free keywords were used to search relevant articles without restrictions on regions, publication types, or languages. The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Odds ratios (ORs) with 95% confidence intervals (CIs) of 5-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and hazard ratios (HRs) with 95% CIs of OS were calculated using a random- or fixed-effects model.

Results:
This meta-analysis included 17 retrospective cohort studies with 5880 patients, of whom 3167 underwent additional surgery and 2713 underwent non-gastrectomy. We found that patients receiving additional gastrectomy had better 5-year OS (OR = 3.63, 95% CI = 3.05–4.31), DSS (OR = 3.22, 95% CI = 2.22–4.66), and DFS (OR = 4.39, 95% CI = 1.78–10.82) outcomes than those receiving non-gastrectomy treatments. The pooled HR also showed that gastrectomy following non-curative ESD significantly improved OS (HR = 0.40, 95% CI = 0.33–0.48). In addition, elderly patients benefited from additional surgery in consideration of the 5-year OS (HR = 0.54, 95% CI = 0.41–0.72).

Conclusions:
Compared with non-gastrectomy treatments, additional surgery offered better long-term survival outcomes for patients with EGC who underwent non-curative ESD.
Stereotactic Body Radiation Therapy for Sarcoma Pulmonary Metastases
Authors: Asha Wafa , Koro Sami , Mayo Zachary , Yang Kailin , Halima Ahmed , Scott Jacob , Scarborough Jessica , Campbell Shauna R. , Budd G. Thomas , Shepard Dale , Stephans Kevin , Videtic Gregory M. , Shah Chirag 
Published: March 2023

Background:
Lung metastases are the most common form of distant failure for patients diagnosed with sarcoma with metastasectomy considered for some patients with limited metastatic disease and good performance status. Alternatives to surgery such as stereotactic body radiation therapy (SBRT) can be considered, though data are limited. We present outcomes after SBRT for sarcoma lung metastases.

Methods:
Fifty sarcoma patients with 109 lung metastases were treated with SBRT between 2005 and 2021. Outcomes evaluated included local control (LC), overall survival (OS), and toxicity including lung pneumonitis/fibrosis, chest wall toxicity, dermatitis, brachial plexus, and esophageal toxicity. Systemic therapy receipt before and after SBRT was recorded.

Results:
SBRT schedules were divided into 3 cohorts: 30 to 34 Gy/1fx (n=10 [20%]), 48 to 50 Gy/4 to 5fx (n=24[48%]), and 60 Gy/5fx (n=16[32%]). With a median follow-up of 19.5 months, 1/3-year LC rates were 96%/88% and 1/3-year OS 77%/50%, respectively. There was no differences between the 3 regimens in terms of LC, OS, or toxicity. Size >4 cm was a predictor of worse LC (P=0.031) and worse OS (P= 0.039) on univariate analysis. The primary pattern of failure was new metastases (64%) of which the majority were in the contralateral lung (52%). One-year chemotherapy-free survival was 85%. Overall, 76% of patients did not require chemotherapy initiation or change of chemotherapy regimen after lung SBRT. Toxicity was reported in 16% of patients overall, including 25%, 20%, and 14% in the 30 to 34 Gy/1fx, 48 to 50 Gy/4 to 5fx, and 60 Gy/5fx cohorts, respectively.

Conclusions:
SBRT outcomes for lung metastases from sarcoma demonstrate high rates of LC and are similar with different dose/fractionation regimens. Lung SBRT is associated with prolonged chemotherapy-free survival. Prospective validation of these results is warranted.
Applications of Volumetric Absorptive Microsampling Technique: A Systematic Critical Review
Authors: Dodeja Prerna , Giannoutsos Spiros , Caritis Steve , Venkataramanan Raman 
Published: March 2023

Background:
Microsampling is a technique that utilizes a very small volume of biological matrix, typically less than 50 µL, for quantitatively analyzing chemicals, drugs, and biologics. The use of filter paper for blotting blood samples, usually referred to “Dried Blood Spots”, is an example of a microsampling approach, which has been established since the early 1960s. However, non-homogeneous sample spread, the influence of hematocrit, improper volume measurement, and environmental degradation are major bottlenecks to the widespread adoption of this technique in routine clinical sample analysis. Novel methods have overcome several of these issues; however, assays using these microsampling tools involve variable steps/approaches.

Methods:
A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years.

Results:
The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized. This review focuses on VAMS and elaborates on bioanalytical factors, method validation steps, and scope of this technique in clinical practice.

Conclusions:
The promising microsampling method VAMS is especially suited for conducting pharmacokinetic studies with very small volumes of blood, especially in special patient populations. Clinical validation of every VAMS assay must be conducted prior to the routine practical implementation of this method.
Development of a Therapeutic Drug Monitoring Strategy for the Optimization of Vincristine Treatment in Pediatric Oncology Populations in Africa
Authors: Van der Heijden Lisa T. , Nijstad A. Laura , Uittenboogaard Aniek , Beijnen Jos H. , Dorlo Thomas P.C. , Kaspers Gertjan J.L. , Huitema Alwin D.R. 
Published: March 2023

Background:
Recent studies have reported ethnic differences in vincristine exposure and outcomes such as toxicity. This resulted in the hypothesis of subtherapeutic dosing in African children. To optimize individual treatment, a strategy to identify subtherapeutic exposure using therapeutic drug monitoring is essential. The aim of the current study was to develop a strategy for therapeutic drug monitoring of vincristine in African children to meet the following criteria: (1) identify patients with low vincristine exposure with sufficient sensitivity (>70%), (2) determine vincristine exposure with a limited sampling strategy design of 3 samples, and (3) allow all samples to be collected within 4 hours after administration.

Methods:
An in silico simulation study was performed using a previously described population pharmacokinetic model and real-life demographic dataset of Kenyan and Malawian pediatric oncology patients. Two different therapeutic drug monitoring strategies were evaluated: (1) Bayesian approach and (2) pharmacometric nomogram. The sampling design was optimized using the constraints described above. Sensitivity analysis was performed to investigate the influence of missing samples, erroneous sampling times, and different boundaries on the nomogram weight bands.

Results:
With the Bayesian approach, 43.3% of the estimated individual exposure values had a prediction error of ≥20% owing to extremely high shrinkage. The Bayesian approach did not improve with alternative sampling designs within sampling constraints. However, the pharmacometric nomogram could identify patients with low vincristine exposure with a sensitivity, specificity, and accuracy of 75.1%, 76.4%, and 75.9%, respectively. The pharmacometric nomogram performed similarly for different weight bands.

Conclusions:
The pharmacometric nomogram was able to identify patients with low vincristine exposure with high sensitivity, with 3 blood samples collected at 1, 1.5, and 4 hours after administration. Missing samples should be avoided, and the 3 scheduled samples should be collected within 15, 5, and 15 minutes of 1, 1.5, and 4 hours after administration, respectively.