bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Biology of the Pituitary Adenoma
Authors: Melmed Shlomo , Kaiser Ursula B , Lopes M Beatriz , Bertherat Jerome , Syro Luis V , Raverot Gerald , Reincke Martin , Johannsson Gudmundur , Beckers Albert , Fleseriu Maria , Giustina Andrea , Wass John A H , Ho Ken K Y 
Published: April 2022

AbstractAll endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in 10% of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intrapituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one-thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas, and particularly their benign nature, stands in marked contrast to other tumors of the endocrine system, such as thyroid and neuroendocrine tumors.
A Novel Homozygous MC2R Variant Leading to Type-1 Familial Glucocorticoid Deficiency
Authors: Mohammed Idris , Haris Basma , Hussain Khalid 
Published: April 2022

Abstract

Context
Type 1 familial glucocorticoid deficiency (FGD) (OMIM #607397) is a rare autosomal recessive disorder due to mutations in melanocortin-2-receptor (MC2R) gene encoding the G protein-coupled adrenocorticotropic (ACTH) transmembrane receptor.

Objective
The aim of the study is to describe 2 siblings born to a healthy consanguineous family presenting with clinical and biochemical features of FGD, harboring a novel homozygous MC2R variant.

Methods
Both patients are siblings born at term via normal delivery with normal birth weights. The first sibling presented with symptoms of hypoglycemia, repeated episodes of infections starting from 2 days of age. At 18 months of age, low serum cortisol was found, and he was started on hydrocortisone replacement therapy. The second sibling developed hypoglycemia on day 1 after birth, investigations revealed low serum sodium and cortisol levels and was also commenced on hydrocortisone treatment. Whole exome sequencing (WES) and in vitro functional studies on cell line transfected with wild-type and mutant plasmid clones were undertaken.

Results
WES revealed a novel homozygous missense mutation c.326T&gt;A, p.Leu109Gln in the MC2R gene. In-silico prediction tools predicted the effect of this mutation to be deleterious. In vitro study using HEK293 cells transfected with MC2R wild-type and mutant clones showed a defect in protein expression and cAMP generation when stimulated with ACTH.

Conclusion
Homozygous semiconserved p.Leu109Gln mutation disrupts cAMP production and MC2R protein expression leading to ACTH resistance. This study provides additional evidence that this novel pathogenic variant in MC2R results in FGD phenotypes.
Approach to the Medical Treatment of Epilepsy
Authors: Brigo Francesco , Marson Anthony 
Published: April 2022

ABSTRACT

PURPOSE OF REVIEW
This article discusses the use of antiseizure medications in the treatment of focal and generalized epilepsies using an evidence-based approach.

RECENT FINDINGS
In recent years, several new antiseizure medications with differing mechanisms of action have been introduced in clinical practice, and their efficacy and safety has been evaluated in randomized controlled clinical trials. Currently, all antiseizure medications can prevent seizure occurrence, but they have no proven disease-modifying or antiepileptogenic effects in humans. The choice of therapy should integrate the best available evidence of efficacy, tolerability, and effectiveness derived from clinical trials with other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences. After the failure of a first antiseizure medication, inadequate evidence is available to inform policy. An alternative monotherapy (especially if the failure is because of adverse effects) or a dual therapy (especially if failure is because of inadequate seizure control) can be used.

SUMMARY
Currently, several antiseizure medications are available for the treatment of focal or generalized epilepsies. They differ in mechanisms of action, frequency of administration, and pharmacologic properties, with a consequent risk of pharmacokinetic interactions. Major unmet needs remain in epilepsy treatment. A substantial proportion of patients with epilepsy continue to experience seizures despite two or more antiseizure medications, with a negative impact on quality of life. Therefore, more antiseizure medications that could provide higher seizure control with good tolerability and that could positively affect the underlying disease are needed.
Surgical Treatments for Epilepsy
Authors: Culler George W. , Jobst Barbara C. 
Published: April 2022

ABSTRACT

PURPOSE OF REVIEW
More than 20 new antiseizure medications have been approved by the US Food and Drug Administration (FDA) in the past 3 decades; however, outcomes in newly diagnosed epilepsy have not improved, and epilepsy remains drug resistant in up to 40% of patients. Evidence supports improved seizure outcomes and quality of life in those who have undergone epilepsy surgery, but epilepsy surgery remains underutilized. This article outlines indications for epilepsy surgery, describes the presurgical workup, and summarizes current available surgical approaches.

RECENT FINDINGS
Class I evidence has demonstrated the superiority of resective surgery compared to medical therapy for seizure control and quality of life in patients with drug-resistant epilepsy. The use of minimally invasive options, such as laser interstitial thermal therapy and stereotactic radiosurgery, are alternatives to resective surgery in well-selected patients. Neuromodulation techniques, such as responsive neurostimulation, deep brain stimulation, and vagus nerve stimulation, offer a suitable alternative, especially in those where resective surgery is contraindicated or where patients prefer nonresective surgery. Although neuromodulation approaches reduce seizure frequency, they are less likely to be associated with seizure freedom than resective surgery.

SUMMARY
Appropriate patients with drug-resistant epilepsy benefit from epilepsy surgery. If two well-chosen and tolerated medication trials do not achieve seizure control, referral to a comprehensive epilepsy center for a thorough presurgical workup and discussion of surgical options is appropriate. Mounting Class I evidence supports a significantly higher chance of stopping disabling seizures with surgery than with further medication trials.
RNA-binding FMRP and Staufen sequentially regulate the Coracle scaffold to control synaptic glutamate receptor and bouton development
Authors: Song Chunzhu , Leahy Shannon N. , Rushton Emma M. , Broadie Kendal 
Published: April 2022

ABSTRACT
Both mRNA-binding Fragile X mental retardation protein (FMRP; Fmr1) and mRNA-binding Staufen regulate synaptic bouton formation and glutamate receptor (GluR) levels at the Drosophila neuromuscular junction (NMJ) glutamatergic synapse. Here, we tested whether these RNA-binding proteins act jointly in a common mechanism. We found that both dfmr1 and staufen mutants, and trans-heterozygous double mutants, displayed increased synaptic bouton formation and GluRIIA accumulation. With cell-targeted RNA interference, we showed a downstream Staufen role within postsynaptic muscle. With immunoprecipitation, we showed that FMRP binds staufen mRNA to stabilize postsynaptic transcripts. Staufen is known to target actin-binding, GluRIIA anchor Coracle, and we confirmed that Staufen binds to coracle mRNA. We found that FMRP and Staufen act sequentially to co-regulate postsynaptic Coracle expression, and showed that Coracle, in turn, controls GluRIIA levels and synaptic bouton development. Consistently, we found that dfmr1, staufen and coracle mutants elevate neurotransmission strength. We also identified that FMRP, Staufen and Coracle all suppress pMad activation, providing a trans-synaptic signaling linkage between postsynaptic GluRIIA levels and presynaptic bouton development. This work supports an FMRP–Staufen–Coracle–GluRIIA–pMad pathway regulating structural and functional synapse development.
Temporal and spatially controlled APP transgene expression using Cre-dependent alleles
Authors: Koller Emily J. , Comstock Melissa , Bean Jonathan C. , Escobedo Gabriel , Park Kyung-Won , Jankowsky Joanna L. 
Published: April 2022

ABSTRACT
Although a large number of mouse models have been made to study Alzheimer's disease, only a handful allow experimental control over the location or timing of the protein being used to drive pathology. Other fields have used the Cre and the tamoxifen-inducible CreER driver lines to achieve precise spatial and temporal control over gene deletion and transgene expression, yet these tools have not been widely used in studies of neurodegeneration. Here, we describe two strategies for harnessing the wide range of Cre and CreER driver lines to control expression of disease-associated amyloid precursor protein (APP) in modeling Alzheimer's amyloid pathology. We show that CreER-based spatial and temporal control over APP expression can be achieved with existing lines by combining a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder using a Cre-to-tTA converter line. We then describe a new mouse line that places APP expression under direct control of Cre recombinase using an intervening lox-stop-lox cassette. Mating this allele with a CreER driver allows both spatial and temporal control over APP expression, and with it, amyloid onset.
This article has an associated First Person interview with the first author of the paper.
Endometrial organoids derived from Mayer–Rokitansky–Küster–Hauser syndrome patients provide insights into disease-causing pathways
Authors: Brucker Sara Y. , Hentrich Thomas , Schulze-Hentrich Julia M. , Pietzsch Martin , Wajngarten Noel , Singh Anjali Ralhan , Rall Katharina , Koch André 
Published: April 2022

ABSTRACT
The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focuses on DNA-sequencing efforts and, so far, has been unable to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point to potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.
Upregulated flotillins and sphingosine kinase 2 derail AXL vesicular traffic to promote epithelial-mesenchymal transition
Authors: Genest Mallory , Comunale Franck , Planchon Damien , Govindin Pauline , Noly Dune , Vacher Sophie , Bièche Ivan , Robert Bruno , Malhotra Himanshu , Schoenit Andreas , Tashireva Liubov A. , Casas Josefina , Gauthier-Rouvière Cécile , Bodin Stéphane 
Published: April 2022

ABSTRACT
Altered endocytosis and vesicular trafficking are major players during tumorigenesis. Flotillin overexpression, a feature observed in many invasive tumors and identified as a marker of poor prognosis, induces a deregulated endocytic and trafficking pathway called upregulated flotillin-induced trafficking (UFIT). Here, we found that in non-tumoral mammary epithelial cells, induction of the UFIT pathway promotes epithelial-to-mesenchymal transition (EMT) and accelerates the endocytosis of several transmembrane receptors, including AXL, in flotillin-positive late endosomes. AXL overexpression, frequently observed in cancer cells, is linked to EMT and metastasis formation. In flotillin-overexpressing non-tumoral mammary epithelial cells and in invasive breast carcinoma cells, we found that the UFIT pathway-mediated AXL endocytosis allows its stabilization and depends on sphingosine kinase 2, a lipid kinase recruited in flotillin-rich plasma membrane domains and endosomes. Thus, the deregulation of vesicular trafficking following flotillin upregulation, and through sphingosine kinase 2, emerges as a new mechanism of AXL overexpression and EMT-inducing signaling pathway activation.
Oh, snap! A within-wing sonation in black-tailed trainbearers
Authors: Rico-Guevara Alejandro , Echeverri-Mallarino Laura , Clark Christopher J. 
Published: April 2022

ABSTRACT
Vertebrates communicate through a wide variety of sounds, but few mechanisms of sound production, besides vocalization, are well understood. During high-speed dives, male trainbearer hummingbirds (Lesbia spp.) produce a repeated series of loud snaps. Hypotheses for these peculiar sounds include the birds employing their elongated tails and/or striking their wings against each other. Each snap to human ears seems like a single acoustic event, but sound recordings revealed that each snap is actually a couplet of impulsive, atonal sounds produced ∼13 ms apart. Analysis of high-speed videos refutes these previous hypotheses, and furthermore suggests that this sonation is produced by a within-wing mechanism – each instance of a sound coincided with a distinctive pair of deep wingbeats (with greater stroke amplitude, measured for one display sequence). Across many displays, we found a tight alignment between a pair of stereotyped deep wingbeats (in contrast to shallower flaps across the rest of the dive) and patterns of snap production, evidencing a 1:1 match between these sonations and stereotyped kinematics. Other birds including owls and poorwills are reported to produce similar sounds, suggesting that this mechanism of sound production could be somewhat common within birds, yet its physical acoustics remain poorly understood.
Heat Therapy Can Improve Hepatic Mitochondrial Function and Glucose Control
Authors: Johnson Chelsea N. , Jensen Reilly S. , Von Schulze Alex T. , Geiger Paige C. 
Published: April 2022

ABSTRACT
This review proposes the novel hypothesis that heat can be used as an alternative therapy to exercise to improve hepatic mitochondrial function and glucose regulation in patients with non-alcoholic fatty liver disease (NAFLD). Although exercise has proven benefits in treating NAFLD, barriers to exercise in the majority of patients necessitate an alternative method of treatment.
SCUBA Diver’s Knee: A Case Report
Authors: Klass Scott , Burton Adam , Price Chane 
Published: April 2022

Abstract
With more than 9 million recreational certified self-contained underwater breathing apparatus divers in the United States, clinicians should be aware of the unique diving-related injuries. One of the most common diving-related injuries is type 1 decompression sickness, or “the bends.” The bends commonly manifest as localized joint pain, most often occurring within 24 h of surfacing and resolving over the following 1 to 2 d. We report a unique case of a patient who experienced an exacerbation of musculoskeletal joint pain following initial recovery. This 35-year-old man had nearly complete resolution of his joint pain following the bends, then developed severe right knee pain with swelling after a high-volume lower body workout. Following unremarkable imaging and unsuccessful conservative treatment, ultrasound-guided aspiration of his right knee was performed, which resolved the patient's symptoms. This case highlights a unique presentation of the bends and demonstrates a potentially beneficial treatment if recurrence of the bends is suspected.
An Overview of Blood Flow Restriction Physiology and Clinical Considerations
Authors: Martin Peter Mitchell , Bart Ryan M. , Ashley Robert L. , Velasco Teonette , Wise Sean R. 
Published: April 2022

Abstract
The utilization of blood flow restriction has garnished considerable attention due to its widespread application and benefits that include strength enhancement, muscle hypertrophy, and increased level of function for specific populations. Blood flow restriction induces a hypoxic environment within a muscle group, initiating a metabolic cascade that stimulates muscle protein synthesis, altered gene regulation of muscle satellite cells, and increased muscle fiber recruitment, ultimately resulting in improved strength and endurance. When using blood flow restriction, consideration of the individual patient, occlusion pressure, cuff width, and cuff size are paramount. Blood flow restriction has been proven to be a consistently safe and effective tool for augmenting rehabilitative regimens for the upper and lower extremity.
A feasibility pilot study of the effects of neurostimulation on swallowing function in Parkinson’s Disease
Authors: Sasegbon Ayodele , Hammerbeck Ulrike , Michou Emilia , Cheng Ivy , Zhang Mengqing , James Charlotte , Hamdy Shaheen 
Published: April 2022

Introduction: Dysphagia often occurs during Parkinson’s disease (PD) and can have severe consequences. Recently, neuromodulatory techniques have been used to treat neurogenic dysphagia. Here we aimed to compare the neurophysiological and swallowing effects of three different types of neurostimulation, 5 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS and pharyngeal electrical stimulation (PES) in patients with PD. Method: 12 PD patients with dysphagia were randomised to receive either 5 Hz rTMS, 1 Hz rTMS, or PES. In a cross-over design, patients were assigned to one intervention and received both real and sham stimulation. Patients received a baseline videofluoroscopic (VFS) assessment of their swallowing, enabling penetration aspiration scores (PAS) to be calculated for: thin fluids, paste, solids and cup drinking. Swallowing timing measurements were also performed on thin fluid swallows only. They then had baseline recordings of motor evoked potentials (MEPs) from both pharyngeal and (as a control) abductor pollicis brevis (APB) cortical areas using single-pulse TMS. Subsequently, the intervention was administered and post interventional TMS recordings were taken at 0 and 30 minutes followed by a repeat VFS within 60 minutes of intervention. Results: All interventions were well tolerated. Due to lower than expected recruitment, statistical analysis of the data was not undertaken. However, with respect to PAS swallowing timings and MEP amplitudes, there was small but visible difference in the outcomes between active and sham. Conclusion: PES, 5 Hz rTMS and 1 Hz rTMS are tolerable interventions in PD related dysphagia. Due to small patient numbers no definitive conclusions could be drawn from the data with respect to individual interventions improving swallowing function and comparative effectiveness between interventions. Larger future studies are needed to further explore the efficacy of these neuromodulatory treatments in Parkinson’s Disease associated dysphagia.
Prevalence of and maternal factors associated with anaemia in pregnant women at antenatal care booking in Tamale, Ghana: a cross-sectional study
Authors: Opare-Asamoah Kwame , Majeed Saeed F , Darcha Rosina , Anueka-Toah Leleta Asuka , Korankye Esther Amoabeng 
Published: April 2022

Background/AimsAnaemia in pregnancy is a severe public health problem in low- and middle-income countries with consequences for both pregnant women and babies. Prevalence rates and associated factors in most Ghanaian communities are unknown. This study was conducted to determine the prevalence of anaemia and related factors at antenatal care booking among pregnant Ghanaian women in an urban setting.MethodsThis facility-based cross-sectional study was conducted among pregnant women reporting for booking at the antenatal clinic of the Tamale Central Hospital in Ghana. A self-designed data collection tool was used and the anaemic status of participants was determined using packed cell volume cut-off (<30.0%). Univariate and multivariate logistic regression analyses were conducted to determine the association between participants' study variables and anaemia.ResultsA total of 606 pregnant women with a mean age of 27.7±5.4 years took part in the study. The prevalence of anaemia was 39.6%. Univariate analysis revealed that pregnant women aged 26–30 years (P=0.01) or >30 years (P<0.001), those who reported for booking in their first trimester of pregnancy (P=0.0043) and those who reported for booking during their second trimester (P=0.0011) were significantly associated with anaemia. In multivariate analysis, only women reporting for booking in their second trimester of pregnancy were significantly associated with anaemia (adjusted odds ratio: 1.8, P<0.001).ConclusionsThe prevalence of anaemia at booking among pregnant Ghanaian urban dwellers remains relatively high and calls for improved education on maternal health, most notably on the need to report early for booking at antenatal facilities to improve both maternal and infant birth outcomes.