bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline Sequencing Improves Tumor-Only Sequencing Interpretation in a Precision Genomic Study of Patients With Pediatric Solid Tumor
Authors: Schienda Jaclyn , Church Alanna J. , Corson Laura B. , Decker Brennan , Clinton Catherine M. , Manning Danielle K. , Imamovic-Tuco Alma , Reidy Deirdre , Strand Gianna R. , Applebaum Mark A. , Bagatell Rochelle , DuBois Steven G. , Glade-Bender Julia L. , Kang Wenjun , Kim AeRang , Laetsch Theodore W. , Macy Margaret E. , Maese Luke , Pinto Navin , Sabnis Amit J. , Schiffman Joshua D. , Colace Susan I. , Volchenboum Samuel L. , Weiser Daniel A. , Nowak Jonathan A. , Lindeman Neal I. , Janeway Katherine A. , Crompton Brian D. , Kamihara Junne 
Published: December 2021

PURPOSE Molecular tumor profiling is becoming a routine part of clinical cancer care, typically involving tumor-only panel testing without matched germline. We hypothesized that integrated germline sequencing could improve clinical interpretation and enhance the identification of germline variants with significant hereditary risks. MATERIALS AND METHODS Tumors from pediatric patients with high-risk, extracranial solid malignancies were sequenced with a targeted panel of cancer-associated genes. Later, germline DNA was analyzed for a subset of these genes. We performed a post hoc analysis to identify how an integrated analysis of tumor and germline data would improve clinical interpretation. RESULTS One hundred sixty participants with both tumor-only and germline sequencing reports were eligible for this analysis. Germline sequencing identified 38 pathogenic or likely pathogenic variants among 35 (22%) patients. Twenty-five (66%) of these were included in the tumor sequencing report. The remaining germline pathogenic or likely pathogenic variants were single-nucleotide variants filtered out of tumor-only analysis because of population frequency or copy-number variation masked by additional copy-number changes in the tumor. In tumor-only sequencing, 308 of 434 (71%) single-nucleotide variants reported were present in the germline, including 31% with suggested clinical utility. Finally, we provide further evidence that the variant allele fraction from tumor-only sequencing is insufficient to differentiate somatic from germline events. CONCLUSION A paired approach to analyzing tumor and germline sequencing data would be expected to improve the efficiency and accuracy of distinguishing somatic mutations and germline variants, thereby facilitating the process of variant curation and therapeutic interpretation for somatic reports, as well as the identification of variants associated with germline cancer predisposition.
Current Iodine Status in Japan: A Cross-sectional Nationwide Survey of Schoolchildren, 2014-2019
Authors: Fuse Yozen , Ito Yoshiya , Shishiba Yoshimasa , Irie Minoru 
Published: December 2021

AbstractContextJapan has been regarded as a long-standing iodine-sufficient country without iodine fortification; however, data on nationwide iodine status are lacking.ObjectiveThis study aimed to characterize the iodine status in Japan.MethodsFrom 2014 through 2019, a nationwide school-based survey was conducted across all districts in Japan. Urinary iodine concentration (UIC), creatinine (Cr) concentration, and anthropometry were assessed in healthy school-aged children (SAC) aged 6 to 12 years. Their iodine status is regarded as generally representative of the nation’s iodine status.ResultsA total of 32 025 children participated. The overall median UIC was 269 μg/L, which was within the World Health Organization’s adequacy range. There was a regional difference in UIC values within 14 regions, and the lowest and highest median UICs were found in Tanegashima Island (209 μg/L) and Nakashibetsu, Hokkaido (1071 μg/L), respectively. The median UIC ≥ 300 μg/L was observed in 12 of 46 regions. By using estimated 24-hour urinary iodine excretion (UIE), the prevalence of SAC exceeding the upper tolerable limit of iodine for Japanese children was from 5.2% to 13.7%. The UIC values did not change with age, body surface area and body mass index percentile, whereas the Cr concentration simultaneously increased suggesting the effect of urinary creatinine on UI/Cr and estimated 24-hour UIE values.ConclusionsThe iodine intake of Japanese people is adequate, but in some areas it is excessive. The incidence and prevalence of thyroid disorders associated with iodine intake should be obtained, especially in the areas where high amounts of iodine are consumed.
Incidence and Risk Factors of Mechanical Complications After Posterior-Based Osteotomies for Correction of Moderate to Severe Adult Cervical Deformity: 1-Year and 2-Year Follow-up
Authors: Lau Darryl , Joshi Rushikesh S. , Haddad Alexander F. , Deviren Vedat , Ames Christopher P. 
Published: December 2021

BACKGROUND:
Rigid cervical deformity (CD) requires multilevel and/or high-grade osteotomies and long-construct fusions to achieve adequate correction. The incidence of mechanical complications (MCs) remains incompletely studied.

OBJECTIVE:
To define the incidence and risk factors for MC.

METHODS:
A retrospective review of consecutive patients with CD who underwent correction from 2010 to 2018 was performed. Inclusion criteria were cervical kyphosis >20° and/or cervical sagittal vertical axis (cSVA) >4 cm. MCs (junctional kyphosis/failure, pseudarthrosis, and implant failure) and reoperation at 1 and 2 yr were examined.

RESULTS:
Eighty-three patients were included. The mean age was 63.4 yr, and 61.0% were female. Fifty-three percent underwent 3-column osteotomies. After surgery, cervical parameters were significantly improved: cSVA (6.2 vs 3.8 cm, P < .001), cervical lordosis (6.3 vs −8.3°, P < .001), cervical scoliosis (CS) (6.5 vs 2.2°, P < .001), and T1 slope (41.7 vs 36.3°, P = .007). The MC rate was 28.9%: junctional (18.1%), implant (16.9%), and pseudarthrosis (10.8%). MC rates at 1 and 2 yr were 14.5% and 25.5%, respectively: junctional (9.6% and 17.6%), implant (9.6% and 17.6%), and pseudarthrosis (2.4% and 7.8%). The overall reoperation rate was 24.1%: 14.5% at 1 yr and 19.6% at 2 yr. Body mass index (BMI) (P = .015) and preoperative CS (P = .040) were independently associated with higher odds of MC. Receiver operating characteristic curves defined CS >5° to be the threshold of risk for MCs and reoperation.

CONCLUSION:
Correction of CD is effective by posterior-based osteotomes, but MCs are relatively high at 1 and 2 yr. BMI >30 and preoperative CS >5° predispose patients for MC and reoperation.
Feasibility of Magnetic Resonance–Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy
Authors: Wathen Connor , Yang Andrew I. , Hitti Frederick L. , Henry Lenora , Chaibainou Hanane , Baltuch Gordon H. 
Published: December 2021

BACKGROUND:
Magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy is a rapidly evolving therapy for the treatment of essential tremor. Although the skull is a major determinant of the delivery of acoustic energy to the target, how the presence of a prior craniotomy must be accounted for during lesioning is unclear.

OBJECTIVE:
To demonstrate novel application of this therapeutic option in a patient with a history of prior craniotomies for unrelated intracranial pathologies.

METHODS:
A 55-yr-old man with a history of right frontal craniotomy for resection of a colloid cyst underwent a left ventrointermedius nucleus thalamotomy through MRgFUS. The prior craniotomy flap was not excluded in the treatment plan; however, all bony defects and hardware were marked as “no-pass” regions. Clinical outcomes were collected at the 6-mo follow-up.

RESULTS:
Transducer elements whose acoustic paths would have been altered by the craniotomy defect were turned off. Sonications reaching lesional temperatures of up to 56°C were successfully delivered. The procedure was well-tolerated, without any persistent intra-ablation or postablation adverse effects. The presence of a lesion was confirmed on MRI, which was associated with a significant reduction in the patient's tremor that was sustained at the 6-mo follow-up.

CONCLUSION:
This case demonstrates the safety and efficacy of MRgFUS thalamotomy in a patient with prior craniotomies and highlights our strategy for acoustic lesioning in this setting.
2-(4-Nitrophenyl)-1H-indolyl-3-methyl Chromophore: A Versatile Photocage that Responds to Visible-light One-photon and Near-infrared-light Two-photon Excitations
Authors: Lin Qianghua , Guo Runzhao , Hamao Kozue , Takagi Ryukichi , Abe Manabu 
Published: December 2021

Abstract
Due to cell damage caused by UV light, photoremovable protecting groups (PPGs) that are removed using visible or near-infrared light are attracting attention. A 2-(4-nitrophenyl)-1H-indolyl-3-methyl chromophore (NPIM) was synthesized as a novel PPG. Various compounds were caged using this PPG and uncaged using visible or near-infrared light. Low cytotoxicity of NPIM indicates that it may be applied in physiological studies.
β-Hydroxy-β-Methylbutyrate Supplementation May Not Enhance Additional Effects of Exercise on Muscle Quality in Older Women
Authors: Osuka Yosuke , Kojima Narumi , Nishihara Ken , Sasai Hiroyuki , Wakaba Kyohsuke , Tanaka Kiyoji , Kim Hunkyung 
Published: December 2021

ABSTRACT

Purpose
The combined treatment effects of nutritional supplementation and exercise on muscle quality (MQ) remain unexamined in individuals at risk for sarcopenia. This secondary analysis aimed to test whether β-hydroxy-β-methylbutyrate (HMB) supplementation enhances the effects of resistance training (RT) on MQ in older women with low muscle mass.

Methods
This randomized, double-blind, placebo-controlled, two-by-two factorial design trial was conducted at the Tokyo Metropolitan Institute of Gerontology. Women age 65–79 yr with a skeletal muscle mass index of <5.7 kg·m−2 were randomly allocated to one of four arms (RT + HMB, RT + placebo, education + HMB, and education + placebo). Participants attended supervised RT sessions twice weekly or education programs every 2 wk and were provided calcium-HMB (1500 mg) or placebo supplements once daily for 12 wk. The main outcomes were changes in functional MQ, assessed by knee extension strength per quadriceps thickness, and compositional MQ, assessed by the echo intensity of the rectus femoris muscle.

Results
Overall, 156 and 149 participants completed baseline and follow-up assessments, respectively. Two-factorial analysis of variance showed no significant interaction of HMB supplementation with RT in terms of functional or compositional MQ. Main-effects analyses revealed that the decline in functional MQ of the group performing RT was smaller by 0.71 N·mm−1 (95% confidence interval, 0.11–1.31) compared with that in the education group. No significant main effects of RT or HMB supplementation on compositional MQ were observed.

Conclusions
HMB supplementation did not enhance the treatment effects of RT for either MQ parameter; however, RT reduced the decline in functional MQ. Thus, adding HMB supplementation to RT is not significantly useful for improving MQ in this population.
Exercise Training Improves Mitochondrial Bioenergetics of Natural Killer Cells
Authors: LIN MING-LU , HSU CHIH-CHIN , FU TIEH-CHENG , LIN YU-TING , HUANG YU-CHIEH , WANG JONG-SHYAN 
Published: December 2021

ABSTRACT

Introduction
Mitochondrial bioenergetics is critical for immune function in natural killer (NK) cell. Physical exercise modulates NK cell functionality, depending on the intensity and type of exercise. This study elucidates how interval and continuous exercise regimens affect the phenotypes and mitochondrial bioenergetics of NK cells.

Methods
Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3-min intervals at 80% and 40% maximal O2, n = 20; age, 22.2 yr; body mass index [BMI], 24.3 kg·m−2) or moderate-intensity continuous training (MICT, sustained 60% maximal O2, n = 20; age, 22.3 yr; BMI, 23.3 kg·m−2) for 30 min·d−1, 5 d·wk−1 for 6 wk or were assigned to a control group that did not receive exercise intervention (n = 20; age, 22.6 yr; BMI, 24.0 kg·m−2). Natural killer cell phenotypes, granule proteins, and mitochondrial oxidative stress/oxidative phosphorylation after graded exercise test (GXT) were measured before and after the various interventions.

Results
Before the intervention, the GXT increased the mobilization of CD57+NK cells into the blood and elevated mitochondrial matrix oxidant burden (MOB) in NK cells, Following the 6 wk of interventions, both HIIT and MICT (i) diminished mobilization of CD57+NK cells into the blood and depressed mitochondrial MOB level in NK cells immediately after GXT, (ii) increased mitochondrial membrane potential and cellular perforin and granzyme B levels in NK cells, and (iii) enhanced the maximal and reserve O2 consumption rates and heightened bioenergetic health index in NK cells. In addition, HIIT increased maximal work rate than those of MICT.

Conclusions
Either HIIT or MICT increases the expressions of cytotoxic granule proteins and depresses mitochondrial MOB elevated by GXT, along with improving mitochondrial bioenergetic functionality in NK cells. Moreover, HIIT is superior to MICT in improving aerobic capacity.
Interventions for Improving Body Composition in Men with Prostate Cancer: A Systematic Review and Network Meta-analysis
Authors: LOPEZ PEDRO , NEWTON ROBERT U. , TAAFFE DENNIS R. , SINGH FAVIL , LYONS-WALL PHILIPPA , BUFFART LAURIEN M. , TANG COLIN , HAYNE DICKON , GALVÃO DANIEL A. 
Published: December 2021

ABSTRACT

Purpose
To perform a systematic review and network meta-analysis to investigate the most effective intervention for improving body composition outcomes in prostate cancer patients during or after treatment.

Methods
A systematic search was undertaken in multiple databases from inception to December 2020. Randomized clinical trials examining the effects of exercise/physical activity and/or nutrition interventions on body composition and body weight measures in prostate cancer patients were included. The primary endpoints were both whole-body and regional fat mass and lean mass measures, with body weight and BMI as secondary outcomes. A frequentist random-effects network meta-analysis was undertaken to examine the clustering effect of intervention modalities or control groups on the outcomes of interest. The study protocol is publicly available on PROSPERO (CRD42020202339).

Results
Fifty articles describing 47 trials (n = 3207) were included. Resistance training and combined resistance and aerobic exercise were the most effective interventions to reduce body fat percentage (−0.9%; 95% confidence interval [CI], −1.4% to −0.3%) and fat mass (−0.5 kg; 95% CI, −0.9 to −0.1 kg), respectively. For whole-body and regional lean mass, combined resistance and aerobic exercise + healthy diet (0.6 kg; 95% CI, 0.1 to 1.0 kg) and resistance training alone (0.7 kg, 95% CI: 0.4 to 1.0 kg) were the best intervention, respectively. A low-fat diet was the most effective for reducing body weight immediately after or at follow-up, while no intervention promoted significant reductions in BMI.

Conclusions
These results indicate that a resistance-based exercise program alone or combined with a general healthy diet are the most effective interventions for improving overall body composition in men with prostate cancer.
Stepper-Based Training Improves Monocyte–Platelet Aggregation and Thrombin Generation in Nonambulatory Hemiplegic Patients
Authors: HUANG SHU-CHUN , HSU CHIH-CHIN , FU TIEH-CHENG , CHEN CARL P. C. , LIAO MING-FENG , HSU CHIEN-YA , WANG JONG-SHYAN 
Published: December 2021

ABSTRACT

Purpose
Nonambulatory stroke patients are extremely sedentary, but most available data concerning exercise training in stroke patients are related to ambulatory patients. This study aimed to investigate the efficacy of stepper-based exercise training on cardiopulmonary fitness, monocyte subtypes, and associated monocyte–platelet aggregates (MPA) and thrombin generation (TrG) in nonambulatory hemiplegic patients with ischemic stroke.

Method
Thirty-eight patients were randomized into exercise training (ET, n = 20) and usual care (UC, n = 18) groups. The ET underwent supervised exercise training (60% peak work rate) using a recumbent stepper for two to four sessions per week and 36 sessions in total. In addition, 12 healthy participants were enrolled as healthy controls. Monocyte characteristics, MPA, and plasma TrG kinetics were determined before and after intervention by flow cytometry and calibrated automated thrombogram® (CAT).

Results
Seventeen and 15 patients completed the protocol in the ET and UC groups. Peak V̇O2 improved in ET (15.7 ± 4.8 vs 18.9 ± 5.3 mL·min−1·kg−1, +20%), so did the phase angle of the hemiplegic limbs. The counts of total MPA and MPA associated with three monocyte subtypes, alongside CD42b expression all declined in ET with subtypes 2 and 1 being the most prominent. Macrophage inflammatory protein 1β (MIP-1 β) level also declined. The TrG kinetics was attenuated after ET by delaying initiation and reducing the rising slope and peak of thrombin production. In UC, no difference was revealed in the pre–post comparison.

Conclusions
Stepper-based ET is feasible in nonambulatory hemiplegic patients and is effective in improving aerobic fitness. Moreover, it decreases heteroaggregation of monocytes with platelets, especially in monocyte subtypes 2 and 1. Thrombin generation was also attenuated. Hence, stepper-based ET may be incorporated in the rehabilitation of nonambulatory hemiplegic patients.
Predicting Noncontact Lower Limb Injury Using Lumbar Morphology in Professional Australian Football and Rugby League Players
Authors: HAJEK MARTIN , WILLIAMS MORGAN D. , BOURNE MATTHEW N. , ROBERTS LLION A. , MORRIS NORMAN R. , SHIELD ANTHONY J. , MINGIN CASSANDRA V. , HEADRICK JONATHON , DUHIG STEVEN J. 
Published: December 2021

ABSTRACT

Introduction
Noncontact lower limb injuries are common within the Australian Football League (AFL) and National Rugby League (NRL). Smaller (<8.5 cm2) lumbar multifidus at the fifth vertebra (LM L5) and larger (>8.2 cm2) quadratus lumborum (QL) cross-sectional area (CSA) have been associated with increased noncontact lower limb injury risk in AFL players. These associations have not been explored in an NRL cohort. This study will attempt to replicate previous research findings by confirming that muscle morphology is associated with noncontact lower limb injury.

Methods
AFL (n = 87) and NRL (n = 151) players underwent LM L2–L5 and QL CSA ultrasound measures during preseason. Each club’s medical staff reported all noncontact lower limb injuries sustained in the subsequent regular season. LM and QL CSA, age, body mass index, and noncontact lower limb injuries were analyzed using multivariable logistic regression.

Results
Seventy-two players sustained a noncontact lower limb injury in the 2020 regular season (AFL = 21, NRL = 51). The multivariable logistic regression (odds ratio (OR) = 1.36; 95% confidence interval (CI), 1.02–1.85; P = 0.038) identified AFL players with larger QL CSA at increased risk of sustaining a noncontact lower limb injury during the regular season, but no relationship was found for LM CSA and noncontact lower limb injuries in the AFL (OR = 1.01; 95% CI, 0.36–2.78; P = 0.591) or NRL (OR = 0.63; 95% CI, 0.29–1.33; P = 0.149).

Conclusions
AFL players who sustained regular season noncontact lower limb injuries had larger QL CSA in preseason tests. No significant associations between either LM L5 CSA or LM L5 to QL ratio and regular season noncontact lower limb injuries were found.
Childhood malnutrition and hypo mineralized molar defects: a cross sectional study
Authors: Atef Abdelsattar Ibrahim Hoda , Abdallah Nasr Rania , Adel Salama Ahmed , Ahmed Amin Aya 
Published: December 2021

Background: Malnutrition is well-known to yield high morbidities and mortalities and considering its consequence on the oral cavity, malnutrition is shown to have pre-eruptive and post-eruptive outcomes. The objective was to assess the prevalence of hypo-mineralized second primary molar (HSPM), molar–incisor hypo-mineralization (MIH) and dental caries in malnourished children as well as addressing the relation between types of malnutrition of the children and their dental morbidities represented in HSPM, MIH and dental caries.Methods:This is a cross sectional analytical study. Malnourished children aged 5-10 years and presented to the Outpatient Clinic of Pediatric Dentistry Department, Faculty of Dentistry, Cairo University were examined for HSPM. MIH using European Academy of Pediatric Dentistry criteria and dental Caries using def/ DMF indices.Results: A consecutive sample (a long six months) of 54 malnourished children were enrolled in the study. Dental caries was a greater dental morbidity in the overweight and obese group. Besides, stunting was a greater risk in HSPM and MIH. There was an association between HSPM and MIH in a considerable percentage of the study group.Conclusions:Malnutrition is a risk factor for dental abnormalities. HSPM could expect the presence of MIH.
Perspectives on Open Science and Scholarly Publishing: a Survey Study Focusing on Early Career Researchers in Europe
Authors: Berezko Oleksandr , Medina Laura M. Palma , Malaguarnera Giulia , Almeida Inês , Żyra Agnieszka , Seang Sothearath , Björnmalm Mattias , Hnatkova Eva , Tata Mathew 
Published: December 2021

Background: The value of Open Science (OS) for the academic community and society has been becoming more evident recently, especially during the COVID-19 pandemic. Nevertheless, significant challenges regarding its implementation arise that are likely to affect researchers, especially those in early career stages. Hence, monitoring early-career researchers’ views, knowledge, and skills on OS and related policies, is crucial for its advancement. The main aim of this exploratory study was to gain new perspectives regarding the awareness of and attitudes towards OS and related practices having in consideration geographical, economic and research career variables. Methods: The survey was conducted during May-August 2020 as part of a collaboration between Eurodoc and the Open Research Europe project. The data from the survey were analyzed by European region, Gross domestic product, Gross domestic expenditure on research and development as a percentage of gross domestic product, field of study, and career stage. Results: The awareness and positive attitude regarding OS, specifically among early-career researchers, is high in Europe. However, there are significant career stage group differences in views and knowledge about OS. Generally, awareness and positive attitude tend to increase with increasing career seniority. Regarding European regions, we spotted three main groups sharing similar awareness levels and attitudes: researchers in Western Europe - the most informed group towards OS; researchers in northern, central, and southern Europe - a moderately informed group with some minor differences; and researchers in eastern Europe - the least informed group, whose opinions deviate the most. Conclusions: We found that there is an “evolution of needs and focus” regarding scientific publishing: researchers in most European regions are in different stages of transition from the competitive to collaborative levels, while researchers in eastern Europe are largely beginning their transition to the competitive level.