bluuebunny/crossref_metadata_2025_split huggingface dataset:
1040 Sleep Hypoventilation with Daytime Eucapnia in COPD May Predict Hypercapnia During Exacerbation
Authors: Tejwani Dimple , Lobrutto Kelly , Naik Sreelatha 
Published: May 2023

Abstract

Introduction
Patients with severe Chronic Obstructive Pulmonary Disease (COPD) are known to be at risk for nocturnal hypoventilation1. We present a case of patient with severe COPD with near normalization of PaCO2 levels after exacerbation but persistent nocturnal hypoventilation.

Report of case(s)
71-year-old woman with COPD Group 4D, on home oxygen, was seen in pulmonary clinic after two hospitalizations for hypercapnic respiratory failure, PcO2 &gt;100 mm Hg requiring acute Noninvasive ventilation (NIV) support. Three weeks after discharge, ABG improved to 7.39/49/140 on 32% Fio2, preventing her from qualifying for long-term home NIV. Sleep study was negative for sleep apnea but showed hypoventilation during sleep. Wake supine transcutaneous CO2 was 45-47 mmHg, increasing to 51-55 mmHg during sleep, worse with supplemental oxygen to 66-67 mm.

Conclusion
Chronic hypercapnia is a poor prognostic indicator in COPD4. In patients with persistent hypercapnia following COPD exacerbation, NIV prolongs time to re-admission or death within 12 months2. Blunting of chemoreceptor response has been noted in hypercapnic patients3, possibly causing subsequent daytime hypercapnia and overt respiratory failure. However, nocturnal hypercapnia is present in some patients and may be a risk factor for profound, life-threatening hypercapnia during exacerbation. Future studies are needed to better phenotype patients such as ours who may be seemingly eucapnic in between exacerbations, but markedly hypercapnic during exacerbation, to determine if there is benefit in treating these patients with NIV as well.

Support (if any)
1. The American Academy of Sleep Medicine Task Force. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. Report of American Academy of Sleep Medicine Task Force. Sleep 1999:22:667-689 2. Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, et al. Effect of home noninvasive ventilation with oxygen therapy vs oxygen therapy alone on hospital readmission or death after an acute COPD exacerbation: a randomized clinical trial. JAMA. 2017:317:2177 3. Scano G,Spinelli A, Duranti R, et al. Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia. Eur Respir J 1995:8:78-85 4. Cooper CB, Waterhouse J, Howard P. Twelve-year clinical study of patients with hypoxic co pulmonale given long term domiciliary oxygen therapy. Thorax 1987:42:105-110
1043 A Rare Case of Non-24-hour Sleep-Wake Rhythm Disorder in A Sighted Patient
Authors: Tu Xinhang , Peng Victor , So Jennifer 
Published: May 2023

Abstract

Introduction
Non-24-hour sleep-wake disorder is a circadian rhythm sleep disorder which causes failure of endogenous circadian rhythm cycles to synchronize to a 24-hour day. Despite an unknown prevalence in sighted people, it's thought to be rare. We present a case of a sighted patient with concurrent bipolar disorder who presented with excessive sleepiness since preadolescence, and was later found to have N24SWD.

Report of case(s)
A 29 year old woman with bipolar disorder presented with excessive daytime sleepiness and irregular sleep schedule since age 12. During her teenage years she often fell asleep at school, and she felt the sleepiness could be associated with psychotropic medication. As she grew up, despite her bipolar disorder was well-controlled, the daytime sleepiness persisted, which caused great challenge concentrating at work and difficulty holding a job. She denies cataplexy, hypnagogic hallucinations, sleep paralysis, or restless legs syndrome symptoms. She had no history of shift work or abnormal movements during sleep. Her bedtime advanced and cycled through a 24-hour period according to sleep diary. Her rise time maintains a consistent interval with her bedtime. Previously she had multiple sleep latency test and polysomnogram, after which she was diagnosed with idiopathic hypersomnia. She was treated with several stimulants without much improvement. She was offered CBT-I but hasn’t gone. She failed trial of a standardized schedule and found it stressful. She tried melatonin and light therapy for a short time without much of success, she was subsequently started on tasimelteon and the clinical response is to be followed.

Conclusion
N24SWD is reportedly rare in the sighted population, with a possible different mechanism from that of the blind population. Behavioral and environmental factors might contribute to the dysynchrony between a normal central circadian pacemaker and a non-24-hour sleep-wake behavioral pattern. Our patient's sleepiness persisted despite her psychiatric disorders were in remission. Altered circadian rhythms are not uncommon in patients with psychiatric disorders, and circadian rhythm dysfunction may be a trait marker of bipolar disease. Some antidepressant are also found to cause potential iatrogenic circadian rhythm sleep disorders. Psychosocial interventions that target stabilizing daily rhythms in patients with concurrent psychiatric illness can be helpful.

Support (if any)
1044 Spinal Muscular Atrophy and Sleep: Double-Trouble
Authors: Willis Aaron , Jefferson Larry , Revana Amee 
Published: May 2023

Abstract

Introduction
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder which leads to progressive muscular weakness and respiratory impairment. Affected patients experience a variety of sleep problems including obstructive sleep apnea, nocturnal hypoventilation, and increased sleep disturbances. As of 2019, the first gene therapy was approved to treat patients with SMA under the age of 2, onasemnogene abeparvovec-xioi (ZolgensmaTM), with expedited approval due to findings of improved motor function and milestone achievement as well as survivability. We describe an unusual case of twins with SMA whom developed worsening obstructive sleep apnea after gene therapy.

Report of case(s)
The patients are a set of 3-year-old male twins with past medical history significant for premature lung disease related to extreme prematurity at 24-weeks and SMA type 2. They were initially referred for polysomnography (PSG) at 1 year of age for evaluation of snoring and as a precaution related to their underlying diagnosis. Physical examination findings were significant for tongue atrophy with fasciculations and generalized muscular weakness which spared the face. Neither twin achieved gross motor milestones of standing or walking to that point. Both patients would receive the gene therapy infusion at 1 year, 8 months with subsequent improvement in hypotonia and ability to ambulate independently. For twin A, baseline PSG at age 1 showed mild obstructive sleep apnea (apnea-hypopnea index (AHI)= 3.24 events per hour) without any signs of hypoxemia or hypoventilation. By comparison, the patient’s post-gene therapy PSG (around 1.5 years post-infusion) at age 3, showed progression to moderate obstruction (obstructive AHI of 6.03 events per hour). For twin B, baseline PSG showed moderate obstructive sleep apnea (AHI=9.09 events per hour) which progressed into the severe range (AHI= 11.90 events per hour) over the same time course.

Conclusion
Sleep-disordered breathing in SMA is a commonly diagnosed entity. While airway obstruction related to hypotonia would be an expected contributor, our case suggests that despite recovery of motor function through use of gene therapy, clinicians should maintain a high level of suspicion for sleep problems with strong consideration for PSG due to the risk of sub-clinical progression of sleep obstruction.

Support (if any)
1045 Resolution of Sexsomnia with Positive Airway Pressure
Authors: Wu Chen , Sajid Mehwish 
Published: May 2023

Abstract

Introduction
Sexsomnia is an infrequently encountered non-rapid eye movement (NREM) arousal disorder that can overlap with obstructive sleep apnea (OSA). Treatment of underlying OSA has been reported to resolve sexsomnia episodes.

Report of case(s)
A 26-year-old overweight man was referred to our Sleep Disorders Center for evaluation of possible “REM sleep behavior disorder.” The patient’s wife reported that he would fondle her breasts while he slept. Episodes began 6 months prior to his referral and occurred once every 1-2 months. During episodes, the patient did not get out of bed. He did not recall the events and denied dream recall. The patient had an infant at home with resultant sleep deprivation. He slept between 5-7 hours a night and stated episodes were more common with decreased total sleep time. Additionally, he reported recent increase in stressors after moving in with his in-laws. On evaluation, patient endorsed bruxism for which he wore a mouth guard. He reported history of sleepwalking in elementary school. He denied excessive daytime sleepiness, snoring, witnessed apneas, gasping arousals, morning headaches, unrefreshing sleep, insomnia, or substance use. He was advised to increase total sleep time and pursue a baseline polysomnogram to evaluate for sleep-disordered breathing. The polysomnogram demonstrated moderate OSA (apnea/hypopnea index of 17). Excessive arousals out of N3 sleep were not reported. He was initiated on auto-titrating positive airway pressure (APAP) and maintained moderate adherence for 2 months. At his follow-up visit, he reported no further episodes of nocturnal fondling after PAP initiation despite persistent sleep deprivation and home stressors.

Conclusion
This case highlights the importance of screening for sleep-disordered breathing which can coexist with NREM parasomnias such as sexsomnia. Even in patients without clear symptoms of sleep-disordered breathing, the evaluation, diagnosis, and treatment of possible OSA could decrease the frequency of sexsomnia episodes. Although this case study was mainly limited by short follow-up duration, the patient’s resolution of sexsomnia in that time demonstrates the importance of treatment of concurrent sleep-related breathing disorders.

Support (if any)
None.
A fish for Phoebe: a new actinopterygian from the Upper Carboniferous Coal Measures of Saddleworth, Greater Manchester, UK, and a revision of Kansasiella eatoni
Authors: Caron Abigail , Venkataraman Vishruth , Tietjen Kristen , Coates Michael 
Published: May 2023

Abstract
The origin of crown Actinopterygii has been dated to near the Devonian-Carboniferous boundary, but poor phylogenetic signal occludes the origin of modern actinopterygian biodiversity. Scarcity of comparative endoskeletal anatomy from this period likely contributes to the uncertainty. For example, only a handful of neurocrania have been described from the Carboniferous period despite an abundance of fossil taxa. Here we present a new actinopterygian, Phoebeannaia mossae gen. et sp. nov., from the Bashkirian Coal Measures of Saddleworth, Greater Manchester, UK, represented by an exceptionally preserved neurocranium and associated dermal bones. Morphological similarities to the Virgilian Kansasiella eatoni prompted comparative study and construction of a new neurocranial character matrix. Subsequent systematic analysis enabled identification of a cluster of similar Late Palaeozoic neurocrania, exploration of trends in braincase evolution across time, and investigation of potential causes of cladistic instability. Our neurocranial dataset reliably places this new specimen on the neopterygian stem near Kansasiella, but it struggles to incorporate extant taxa such as Polypteriformes, leading to uncertainty in branching pattern and inferred neurocranial transformation series. This work triples the number of complete Carboniferous neurocrania described with modern microcomputed tomography and provides a framework for future testing of large-scale hypotheses regarding the diversification and origin of ray-finned fishes.
Three-dimensional Reconstruction and Comparison of Temporomandibular Joint Space Volume Before and After Orthognathic Surgery in Patients with Skeletal Class III Malocclusion With Mandibular Deviation
Authors: Shi Hongli , Sun Xiumei , Xiao Yanju , Li Nannan , Wang Lin , Wu Guomin 
Published: May 2023

Objective:
To look into the association between the degree of deviation and the changing trend in the temporomandibular joint (TMJ) space volume after orthognathic surgery in patients with skeletal Class III malocclusion.

Methods:
Twenty patients having combined orthodontic-orthognathic treatment for skeletal Class III malocclusions with mandibular deviation were chosen, and craniofacial spiral CT was performed before (T0), two weeks after (T1), and six months after (T2) surgery. Using 3D volume reconstruction, further partitioning, and analysis of each domain’s volume changes over time, the TMJ space volume is to be obtained. The differences in changes between groups A (mild deviation group) and B (severe deviation group) were examined to examine the impact of the degree of deviation on the TMJ space volume.

Results:
A statistically significant difference (P<0.05) existed between the postoperative TMJ space volume in group A and the preoperative overall, anterolateral, and anteroinferior space volume; the same difference also existed between the postoperative TMJ space volume in the NDS and the preoperative posterolateral, posteroinferior space volume. In group B, the postoperative TMJ space volume was statistically significant (P<0.05) compared with the preoperative total and anteroinferior space volume in the DS; the difference between the total volume of the T1 stage on the NDS and the total volume of the T0 stage was statistically significant (P<0.05). The two groups showed substantial differences in the space volume changes between the T1-T0 phase and the T2-T1 period.

Conclusion:
Patients with skeletal Class III malocclusion and mandibular deviation after orthognathic surgery see a change in the TMJ space volume. All patient types experience a largely consistent space volume change trend two weeks after surgery, and the degree of mandibular deviation is correlated with the intensity and longevity of the alteration.
Evaluating the Effectiveness of Potential Interventions for Guinea Worm Disease in Dogs in Chad Using Simulations
Authors: Wang Yifan , Perini Tyler , Keskinocak Pinar , Smalley Hannah , Swann Julie , Weiss Adam 
Published: May 2023

ABSTRACTGuinea worm disease (or dracunculiasis) is currently transmitted among dogs in Chad, which presents risks for the human population. We studied how interventions implemented at different levels might reduce the spread of Guinea worm disease (geographically and over time) and what levels of interventions might accelerate elimination. We built a multi-water-source agent-based simulation model to analyze the disease transmission among dogs in Chad, as well as in geographic district clusters, and validated it using local infection data. We considered two interventions: (i) tethering, where infected dogs are kept on a leash during periods of infectivity, and (ii) Abate®, under which the water source is treated to reduce infectivity. Our results showed that elimination (0 dog infections) is most likely achieved within five years with extremely high levels of tethering (95%) and Abate (90%), when intervention levels are uniform across district clusters. We used an optimization model to determine an improved strategy, with intervention levels which minimize the number of dogs newly infected in the sixth year, under limitations on intervention levels across clusters; the number of dogs infected after five years of intervention could be reduced by approximately 220 dogs with an optimized strategy. Finally, we presented strategies that consider fairness based on intervention resource levels and outcomes. Increased tethering and Abate resources above historical levels are needed to achieve the target of Guinea worm disease elimination; optimization methods can inform how best to target limited resources and reach elimination faster.
Relationship between branched chain amino acids and type 2 diabetes: a bidirectional Mendelian Randomization study
Authors: Mosley Jonathan D. , Shi Mingjian , Agamasu David , Vaitinadin Nataraja Sarma , Murthy Venkatesh , Shah Ravi V. , Bagheri Minoo , Ferguson Jane F. 
Published: May 2023

ABSTRACTBackgroundHuman genetic studies suggest that the branched chain amino acids (BCAA) valine, leucine and isoleucine have a causal association with type 2 diabetes. However, inferences are based on analyses of a limited number of genetic loci associated with BCAAs. Whether these conclusions are supported when using instrumental variables for BCAAs that capture a broad set of genetic mechanisms is not known.MethodsWe constructed and validated instrumental variables for each BCAA using large well-powered datasets and tested their association with type 2 diabetes using the two-sample inverse variance weighted (IWV) Mendelian randomization (MR) approach. Sensitivity analyses were performed to ensure the accuracy of the findings. Instrumental variables for type 2 diabetes, fasting insulin and body mass index (BMI) were also tested for associations with BCAA levels.ResultsThere were no significant associations with diabetes for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, −0.28 - 0.62], p=0.45), leucine (beta=0.19 [−0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [−0.54 - 0.59], p=0.94). In contrast, type 2 diabetes was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8×10−9), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5×10−8) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8×10−8). The type 2 diabetes associations were replicated in an independent population, but not in a second population where type 2 diabetes cases were removed, highlighting the consistency and specificity of the association. Similar positive associations were seen for fasting insulin and BMI with the BCAAs. In multivariable MR analyses, type 2 diabetes and fasting insulin had consistent independent associations with each BCAA.ConclusionsThese data suggest that the BCAAs are not mediators of type 2 diabetes risk but are biomarkers of diabetes and higher insulin.
Exploring the common genetic architecture of autism spectrum disorder using a novel multi-polygenic risk score approach
Authors: Schmilovich Zoe , Bourque Vincent-Raphaël , Huguet Guillaume , He Qin , Ross Jay P. , Jean-Louis Martineau , Saci Zohra , Chaumette Boris , Dion Patrick A. , Jacquemont Sébastien , Rouleau Guy A. 
Published: May 2023

ABSTRACTCompared to disorders of similar heritability and contribution of common variants, few genome-wide significant loci have been implicated in autism spectrum disorder (ASD). This undermines the use of polygenic risk scores (PRSs) to investigate the common genetic architecture of ASD. Deconstructing PRS-ASD into its related traits via “developmental deconstruction” could reveal the underlying genetic liabilities of ASD. Using the data of >24k individuals with ASD and >28k of their unaffected family members from the SSC, SPARK, and MSSNG cohorts, we computed the PRSs for ASD and 11 genetically-related traits. We applied an unsupervised learning approach to the ASD-related PRSs to derive “multi-PRSs” that captured their variability in orthogonal dimensions. We found that multi-PRSs captured a similar proportion of genetic risk for ASD in cases versus intrafamilial controls (ORmulti-PRS=1.10, R2=0.501%), compared to PRS-ASD itself (ORPRS-ASD=1.16, R2=0.619%). While multi-PRS dimensions conferred risk for ASD, they had “mirroring” effects on developmental phenotypes among cases with ASD. We posit that this phenomenon may partially account for the paucity of genome-wide significant loci and the clinical heterogeneity of ASD. This approach can serve as a proxy for PRS-ASD in cases where non-overlapping and well-powered GWAS summary statistics are difficult to obtain, or accounting for heterogeneity in a single dimension is preferable. This approach may also capture the overall liability for a condition (i.e.: genetic “P-factor”). Altogether, we present a novel approach to studying the role of inherited, additive, and non-specific genetic risk factors in ASD.
Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID
Authors: Pietzner Maik , Denaxas Spiros , Yasmeen Summaira , Ulmer Maria A. , Nakanishi Tomoko , Arnold Matthias , Kastenmüller Gabi , Hemingway Harry , Langenberg Claudia 
Published: May 2023

ABSTRACTEarly evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses, including common, but non-fatal diseases are scarce, but may help to understand severe COVID-19 among patients at supposedly low risk. Here, we systematically harmonized >12 million primary care and hospitalisation health records from ∼500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID. We identified a total of 679 diseases associated with an increased risk for severe COVID-19 (n=672) and/or Long COVID (n=72) that spanned almost all clinical specialties and were strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we established consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This included a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observed partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis (e.g.,MUC5B,NPNT, andPSMD3) or rheumatoid arthritis (e.g.,TYK2), possibly indicating a segregation of disease mechanisms. Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple – including non-fatal – conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.