bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current clinical management of constitutional delay of growth and puberty
Authors: Gaudino Rossella , De Filippo Gianpaolo , Bozzola Elena , Gasparri Manuela , Bozzola Mauro , Villani Alberto , Radetti Giorgio 
Published: March 2022

Abstract
Background
Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences.

Main text
A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended.

Conclusion
Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Mutational analysis of compound heterozygous mutation p.Q6X/p.H232R in SRD5A2 causing 46,XY disorder of sex development
Authors: Li Liwei , Zhang Junhong , Li Qing , Qiao Li , Li Pengcheng , Cui Yi , Li Shujun , Hao Shirui , Wu Tongqian , Liu Lili , Yin Jianmin , Hu Pingsheng , Dou Xiaowei , Li Shuping , Yang Hui 
Published: March 2022

Abstract
Background
Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration.

Methods
The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography–mass spectrometry (LC–MS) for 5α-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5α-reductase 2 enzyme with testosterone (T) or NADPH.

Results
The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC–MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of SRD5A2 with T or NADPH.

Conclusions
Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.
Epidemiology of traumatic cervical spinal fractures in a general Norwegian population
Authors: Utheim Nils Christian , Helseth Eirik , Stroem Mona , Rydning Paal , Mejlænder-Evjensvold Magnus , Glott Thomas , Hoestmaelingen Christina Teisner , Aarhus Mads , Roenning Paal Andre , Linnerud Hege 
Published: March 2022

Abstract
Background
In Western countries, the typical cervical spine fracture (CS-Fx) patient has historically been a young male injured in a road traffic accident. Recent reports and daily clinical practice clearly indicate a change in the typical patient from a young male to an elderly male or female with comorbidities. This study aimed to establish contemporary population-based epidemiological data of traumatic CS-Fx for use in health-care planning and injury prevention.

Methods
This is a population-based retrospective database study (with prospectively collected data) from the Southeast Norway health region with 3.0 million inhabitants. We included all consecutive cases diagnosed with a CS-Fx between 2015 and 2019. Information regarding demographics, preinjury comorbidities, trauma mechanisms, injury description, treatment, and level of hospital admittance is presented.

Results
We registered 2153 consecutive cases with CS-Fx during a 5-year period, with an overall crude incidence of CS-Fx of 14.9/100,000 person-years. Age-adjusted incidences using the standard population for Europe and the World was 15.6/100,000 person-years and 10.4/100,000 person-years, respectively. The median patient age was 62 years, 68% were males, 37% had a preinjury severe systemic disease, 16% were under the influence of ethanol, 53% had multiple trauma, and 12% had concomitant cervical spinal cord injury (incomplete in 85% and complete in 15%). The most common trauma mechanisms were falls (57%), followed by bicycle injuries (12%), and four-wheel motorized vehicle accidents (10%). The most common upper CS-Fx was C2 odontoid Fx, while the most common subaxial Fx was facet joint Fx involving cervical level C6/C7. Treatment was external immobilization with a stiff neck collar alone in 65%, open surgical fixation in 26% (giving a 3.7/100,000 person-years surgery rate), and no stabilization in 9%. The overall 90-day mortality was 153/2153 (7.1%).

Conclusions
This study provides an overview of the extent of the issue and patient complexity necessary for planning the health-care management and injury prevention of CS-Fx. The typical CS-Fx patient was an elderly male or female with significant comorbidities injured in a low-energy trauma. The overall crude incidences of CS-Fx and surgical fixation of CS-Fx in Southeast Norway were 14.9/100,000 person-years and 3.7/100,000 person-years, respectively.
Formulation of oxybutynin chloride microparticle-loaded suppositories: in vitro characterization and in vivo pharmacokinetic study
Authors: Bedse Anjali , Mahajan Hitendra , Dhamane Suchita 
Published: March 2022

Abstract
Background
Oxybutynin chloride (OXC) is used to treat overactive urinary bladder. OXC is metabolized in the liver to N-desethyloxybutynin, which is mainly responsible for the anticholinergic side effects of OXC. Conventional oxybutynin suppositories formulated earlier have shown most common side effects, such as dry mouth, constipation and serious anticholinergic reaction. Hence the present research work deals with the formulation and characterization of OXC microparticle-loaded mucoadhesive suppositories which may remain adhered in the lower rectum and avoid first pass metabolism. The emulsification–ionic gelation method is employed to prepare OXC microparticles. Two formulation factors at three levels, i.e. polymer concentration and stirring speed, were selected. Sodium alginate (concentration 1–2%) and 1% w/v Carbopol 971P were used to prepare OXC microparticles. OXC microparticles were evaluated for various parameters such as production yield, entrapment efficiency, mucoadhesive strength, shape, size, zeta potential, Fourier Transform Infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, in vitro dissolution studies and stability studies. Suppositories loaded with OXC microparticles were prepared by the fusion method using Poloxamer 188 and propylene glycol and evaluated for various parameters like weight variation, disintegration time, in vitro dissolution study, stability study and pharmacokinetic study.

Results
Results of in vitro characterization revealed that optimized batch of OXC loaded microparticles exhibited production yield 94.024% entrapment efficiency 95.378% and mucoadhesion strength 95.544%, particle size range 764.04–894.13 µm, zeta potential − 14.5 mV, with 0.946 desirability. Consequences of DSC and XRPD evaluation shown that drug was effectively entrapped inside the microparticles. In vitro release studies revealed improvement in drug dissolution as a consequence of its entrapment into microparticles. SEM results showed that micelles were sphere-shaped. On rectal administration of OXC microparticles loaded suppository in male Sprague–Dawley Rats, the relative bioavailability was found 173.72%.

Conclusion
In vivo study elicits rapid increase in absorption of drug from microparticles loaded suppository when compared with the oral formulation and drug loaded suppository in rats. OXC microparticles loaded suppository is novel and promising drug delivery system for rectal administration and may avoid anticholinergic side effects of hepatic metabolite, N-desethyloxybutynin. These rectal drug delivery systems will be advantageous for efficient absorption of drugs and to avoid first pass metabolism.
They like to move it (move it): walking kinematics of balitorid loaches of Thailand
Authors: Crawford Callie H. , Webber-Schultz Amani , Hart Pamela B. , Randall Zachary S. , Cerrato-Morales Cristian , Kellogg Audrey B. , Amplo Haley E. , Suvarnaraksha Apinun , Page Lawrence M. , Chakrabarty Prosanta , Flammang Brooke E. 
Published: March 2022

ABSTRACT
Balitorid loaches are a family of fishes that exhibit morphological adaptations to living in fast flowing water, including an enlarged sacral rib that creates a ‘hip’-like skeletal connection between the pelvis and the axial skeleton. The presence of this sacral rib, the robustness of which varies across the family, is hypothesized to facilitate terrestrial locomotion seen in the family. Terrestrial locomotion in balitorids is unlike that of any known fish: the locomotion resembles that of terrestrial tetrapods. Emergence and convergence of terrestrial locomotion from water to land has been studied in fossils; however, studying balitorid walking provides a present-day natural laboratory to examine the convergent evolution of walking movements. We tested the hypothesis that balitorid species with more robust connections between the pelvic and axial skeleton (M3 morphotype) are more effective at walking than species with reduced connectivity (M1 morphotype). We predicted that robust connections would facilitate travel per step and increase mass support during movement. We collected high-speed video of walking in seven balitorid species to analyze kinematic variables. The connection between internal anatomy and locomotion on land are revealed herein with digitized video analysis, μCT scans, and in the context of the phylogenetic history of this family of fishes. Our species sampling covered the extremes of previously identified sacral rib morphotypes, M1 and M3. Although we hypothesized the robustness of the sacral rib to have a strong influence on walking performance, there was not a large reduction in walking ability in the species with the least modified rib (M1). Instead, walking kinematics varied between the two balitorid subfamilies with a generally more ‘walk-like’ behavior in the Balitorinae and more ‘swim-like’ behavior in the Homalopteroidinae. The type of terrestrial locomotion displayed in balitorids is unique among living fishes and aids in our understanding of the extent to which a sacral connection facilitates terrestrial walking.
Modular lung ventilation in Boa constrictor
Authors: Capano John G. , Boback Scott M. , Weller Hannah I. , Cieri Robert L. , Zwemer Charles F. , Brainerd Elizabeth L. 
Published: March 2022

ABSTRACT
The evolution of constriction and of large prey ingestion within snakes are key innovations that may explain the remarkable diversity, distribution and ecological scope of this clade, relative to other elongate vertebrates. However, these behaviors may have simultaneously hindered lung ventilation such that early snakes may have had to circumvent these mechanical constraints before those behaviors could evolve. Here, we demonstrate that Boa constrictor can modulate which specific segments of ribs are used to ventilate the lung in response to physically hindered body wall motions. We show that the modular actuation of specific segments of ribs likely results from active recruitment or quiescence of derived accessory musculature. We hypothesize that constriction and large prey ingestion were unlikely to have evolved without modular lung ventilation because of their interference with lung ventilation, high metabolic demands and reliance on sustained lung convection. This study provides a new perspective on snake evolution and suggests that modular lung ventilation evolved during or prior to constriction and large prey ingestion, facilitating snakes’ remarkable radiation relative to other elongate vertebrates.
Liver T1 relaxation time of the ‘normal liver’ in healthy Asians: measurement with MOLLI and B1-corrected VFA methods at 3T
Authors: Ghavamian Armin , Liu Cuihong , Kang Bing , Yuan Xianshun , Wang Ximing , Gao Ling , Zhao Xinya 
Published: March 2022

Objectives: Liver T1 is a potential magnetic resonance imaging biomarker for liver diseases. This study aimed to determine the T1 relaxation time of the normal liver (PDFF<5%) in healthy Asian volunteers using modified look-locker inversion recovery (MOLLI) and B1 inhomogeneity-corrected variable flip angle (B1-corrected VFA). Methods: 60 healthy Asian volunteers without focal or diffuse liver disease underwent a liver scan at 3T magnetic resonance. Proton density fat fraction (PDFF) and liver stiffness measurements were applied for the quantification of liver fat and fibrosis. T1 mapping was performed with MOLLI and B1-corrected VFA sequences. Bland-Altman, linear regression, Student t-test, and one-way analysis of variance were used for statistical analysis. Results: The mean T1 relaxation times of the whole liver were 901 ± 34 ms by MOLLI, and 948 ± 29 ms by B1-corrected VFA in healthy volunteers. There was a strong correlation (r = 0.86, p < 0.0001) for liver T1 between two T1 mapping methods. There were significant differences between the right and left lobes in liver T1 relaxation times using both methods (p < 0.05). Gender and Asian ethnic disparities had no impact on liver T1 relaxation times. Conclusion: T1 relaxation times of the normal liver (PDFF<5%) in healthy volunteers were established by MOLLI and B1-corrected VFA T1 mapping methods at 3T. It may provide suitable and robust baseline values for the assessment of liver diseases. Advances in knowledge: Gender and Asian ethnic disparities do not impact liver T1 relaxation time measurements.
Shaming for Tax Enforcement
Authors: Dwenger Nadja , Treber Lukas 
Published: March 2022

We investigate company reactions to the threat of reputational losses. To do so, we leverage the introduction of a naming-and-shaming policy for tax debt enforcement in Slovenia in 2012. The policy was announced four months before its implementation, which allows us to separate responses to the threat of shaming from the responses to actual shaming. Our extensive administrative tax data cover taxes owed and paid for the universe of taxpayers in Slovenia. Based on a quasi-experimental research design, we document that corporations significantly reduce their tax debt in response to the threat of shaming, particularly in industries in which reputational concerns are likely to be important. Self-employed individuals also reduce their tax debt but to a lesser extent. The publication of the first naming-and-shaming list further reduced tax debt among shamed taxpayers. However, the effect of actual shaming is marginal compared with that of the threat of shaming and reduces quickly. Previously compliant taxpayers remained compliant throughout. This paper was accepted by Yan Chen, decision analysis. Funding: This work was supported by Deutscher Akademischer Austauschdienst [Grant 91537728/211483], Deutsche Forschungsgemeinschaft [Grant DW 75/1-1], and Norges Forskningsråd [Grant 314479]. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2021.4295 .
Mis-Nudging Morality
Authors: Morvinski Coby , Saccardo Silvia , Amir On 
Published: March 2022

Morals constrain self-serving behavior. Yet, self-regulation failures in the face of monetary temptation are common at the workplace. To limit such failures, organizations can design environments that limit the temptation to behave self-servingly, nudging workers to uphold their morals. In a series of experiments where participants may be tempted to take excessive pay after exerting effort, we study whether a simple intervention—asking individuals to state the wage they believe should be paid ex ante, before facing the temptation to take excessive compensation—prevents self-serving behavior. In contrast to lay beliefs and the predictions from prior work, we find that such an intervention is not effective, leading to self-serving behavior. However, a more realistic elicitation procedure of the appropriate wage mitigates this effect. These findings contribute to work on the malleability of moral behavior showing that simple interventions thought to effectively mitigate self-serving behavior can prompt individuals to stretch their moral boundaries. They also stress the importance of properly testing interventions that might seem intuitive. This paper was accepted by Yan Chen, behavioral economics and decision analysis. Funding: Financial support from the Israel Science Foundation [Grant 766/19] is gratefully acknowledged. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2022.4344 .
Trends in stroke admissions before, during and post-peak of the COVID-19 pandemic: A one-year experience from the Qatar stroke database
Authors: Akhtar Naveed , Kamran Saadat , Al-Jerdi Salman , Imam Yahia , Joseph Sujatha , Morgan Deborah , Abokersh Mohamed , Uy R. T. , Shuaib Ashfaq 
Published: March 2022

Background
Several reports document a decrease in the rates of stroke hospital admissions during the covid-19 pandemic. There is very little information whether the admission rates will change as the infection is controlled. We report on our rates of admissions before, during and following the peak of covid-19 infections in a prospective database from Qatar.

Methods and results
The stroke admissions in the six months prior to COVID-19 pandemic averaged 229/month. There was a decrease to 157/month in March-June during the peak of the pandemic. In the 6 months following the peak, as covid-19 numbers began to decrease, the average numbers increased back to 192/month. There was an increase in severe ischemic strokes and decreased in functional recovery. The decreased admissions were mainly driven by fewer stroke mimics. Patients presenting with ischemic stroke or cerebral hemorrhage remained unchanged.

Conclusions
Fewer stroke mimics presenting to the hospital can explain the fewer admissions and poor outcome at the height of the covid-19 pandemic. The continued decrease in the number of ischemic stroke and stroke mimic admissions following the pandemic peak requires more study.
A novel autotransfusion device saving erythrocytes and platelets used in a 72 h survival swine model of surgically induced controlled blood loss
Authors: Schreiber Kévin , Decouture Benoit , Lafragette Audrey , Chollet Stéphane , Bruneau Marine , Nicollet Maxence , Wittmann Catherine , Gadrat Francis , Mansour Alexandre , Forest-Villegas Patricia , Gauthier Olivier , Touzot-Jourde Gwenola 
Published: March 2022

Background
The purpose of this study was to develop a swine model of surgically induced blood loss to evaluate the performances of a new autotransfusion system allowing red blood cells and platelets preservation while collecting, washing and concentrating hemorrhagic blood intraoperatively.

Methods
Two types of surgically induced blood loss were used in 12 minipigs to assess system performance and potential animal complications following autotransfusion: a cardiac model (cardiopulmonary bypass) and a visceral model (induced splenic bleeding). Animal clinical and hematological parameters were evaluated at different time-points from before bleeding to the end of a 72-hour post-transfusion period and followed by a post-mortem examination. System performances were evaluated by qualitative and quantitative parameters.

Results
All animals that received the autotransfusion survived. Minimal variations were seen on the red blood cell count, hemoglobin, hematocrit at the different sampling times. Coagulation tests failed to show any hypo or hypercoagulable state. Gross and histologic examination didn’t reveal any thrombotic lesions. Performance parameters exceeded set objectives in both models: heparin clearance (≥ 90%), final heparin concentration (≤ 0.5 IU/mL), free hemoglobin washout (≥ 90%) and hematocrit (between 45% and 65%). The device treatment rate of diluted blood was over 80 mL/min.

Conclusions
In the present study, both animal models succeeded in reproducing clinical conditions of perioperative cardiac and non-cardiac blood loss. Sufficient blood was collected to allow evaluation of autotransfusion effects on animals and to demonstrate the system performance by evaluating its capacity to collect, wash and concentrate red blood cells and platelets. Reinfusion of the treated blood, containing not only concentrated red blood cells but also platelets, did not lead to any postoperative adverse nor thrombogenic events. Clinical and comparative studies need to be conducted to confirm the clinical benefit of platelet reinfusion.