bluuebunny/crossref_metadata_2025_split huggingface dataset:
The onset of large size in Cretaceous marine turtles (Protostegidae) evidenced by new fossil remains from the Valanginian of Colombia
Authors: Cadena Edwin-Alberto , Combita-Romero Diego A 
Published: July 2023

Abstract
The evolution of large size in vertebrates is a fascinating research topic, relevant, for example, for the Cretaceous turtles of the Protostegidae clade, which includes some of the largest turtles to have ever inhabited the Earth. However, there is still limited understanding regarding when and under what conditions large size emerged in this group. Here we describe several limb bones and fossil shell remains from the upper Valanginian, Rosa Blanca Formation of Colombia that, together, shed light on the onset conditions and characteristics of large-size evolution in protostegids. The material, although fragmentary, preserves enough features, such as the sigmoidal curvature of the shaft of the humeri in anterior view and their strong waist, to be attributed to Protostegidae. The fossil turtles described here constitute the largest ever known for the Early Cretaceous worldwide and the oldest record for their group. The ecological and climatic conditions of northern South America during the Late Valanginian are discussed as potential triggers of the emergence of large body size in protostegid turtles.
Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: Dimethyl fumarate and H‐151 downregulate inflammatory cytokines in the cGAS‐STING pathway
Authors: Zamiri Kurosh , Kesari Santosh , Paul Ketema , Hwang Sung Hee , Hammock Bruce , Kaczor‐Urbanowicz Karolina Elżbieta , Urbanowicz Andrzej , Gao Lucy , Whitelegge Julian , Fiala Milan 
Published: July 2023

AbstractIn sporadic amyotrophic lateral sclerosis (sALS), IL‐17A‐ and granzyme‐positive cytotoxic T lymphocytes (CTL), IL‐17A‐positive mast cells, and inflammatory macrophages invade the brain and spinal cord. In some patients, the disease starts following a trauma or a severe infection. We examined cytokines and cytokine regulators over the disease course and found that, since the early stages, peripheral blood mononuclear cells (PBMC) exhibit increased expression of inflammatory cytokines IL‐12A, IFN‐γ, and TNF‐α, as well as granzymes and the transcription factors STAT3 and STAT4. In later stages, PBMCs upregulated the autoimmunity‐associated cytokines IL‐23A and IL‐17B, and the chemokines CXCL9 and CXCL10, which attract CTL and monocytes into the central nervous system. The inflammation is fueled by the downregulation of IL‐10, TGFβ, and the inhibitory T‐cell co‐receptors CTLA4, LAG3, and PD‐1, and, in vitro, by stimulation with the ligand PD‐L1. We investigated in two sALS patients the regulation of the macrophage transcriptome by dimethyl fumarate (DMF), a drug approved against multiple sclerosis and psoriasis, and the cyclic GMP‐AMP synthase/stimulator of interferon genes (cGAS/STING) pathway inhibitor H‐151. Both DMF and H‐151 downregulated the expression of granzymes and the pro‐inflammatory cytokines IL‐1β, IL‐6, IL‐15, IL‐23A, and IFN‐γ, and induced a pro‐resolution macrophage phenotype. The eicosanoid epoxyeicosatrienoic acids (EET) from arachidonic acid was anti‐inflammatory in synergy with DMF. H‐151 and DMF are thus candidate drugs targeting the inflammation and autoimmunity in sALS via modulation of the NFκB and cGAS/STING pathways.
Curiosity, Opportunity, and Luck: Were the 1970s Different?
Authors: Gattinoni Luciano 
Published: July 2023

Control of Breathing Using an Extracorporeal Membrane Lung. By T Kolobow, L Gattinoni, TA Tomlinson, JE Pierce. Anesthesiology 1977; 46:138–41. Reprinted with permission.

Body Position Changes Redistribute Lung Computed-Tomographic Density in Patients with Acute Respiratory Failure. By L Gattinoni, P Pelosi, G Vitale, A Pesenti, L D’Andrea, D Mascheroni. Anesthesiology 1991; 74:15–23. Reprinted with permission.
Dr. Gattinoni’s scientific career was primarily driven by curiosity. His generation was not formally trained, but he was part of a community of young and enthusiastic colleagues who were forging a new discipline: intensive care medicine. The most significant opportunity of Dr. Gattinoni’s career was becoming the research fellow of a visionary genius, Dr. Theodor Kolobow, who focused on extracorporeal carbon dioxide removal after the failure of the first trial on extracorporeal membrane oxygenation. CO2 removal, by allowing control over the intensity of mechanical ventilation, opened the path to “lung rest” to prevent ventilator-induced lung injury. A unique opportunity for research was the spontaneous birth of a network of scientists who became friends in the European Group of Research in Intensive Care Medicine. In this environment, it was possible to develop core concepts such as the “baby lung” and to understand the mechanisms underlying computed tomography–density redistribution in the prone position. Physiology guided us in the 1970s, and understanding mechanisms remains of paramount importance today.
Reconstruction of the Exenterated Orbit with an Island Pericranial Flap: A New Surgical Approach
Authors: Kuehnel Sophia , Grimm András , Bohr Christopher , Hosemann Werner , Weber Rainer , Ettl Tobias , Kuehnel Thomas 
Published: July 2023

Background:
Reconstruction of the bony socket after orbital exenteration is a matter of much debate. Prompt defect closure with a microvascular flap is desirable but involves a major surgical procedure and hence, places considerable burden on the patient. The new surgical technique presented here permits a technically simpler wound closure with fewer complications after orbital exenteration.

Methods:
Between May 2014 and June 2022 in the ENT department of Regensburg University, nine patients underwent exenteration and reconstruction with a pericranial flap. The flap was raised via a broken line incision in the forehead or endoscopically, incised in a roughly croissant-like shape, then introduced into the orbit through a tunnel in the eyebrow. A retrospective analysis of the patients and considerations about determining the size, shape, and vascular supply of the flap are presented.

Results:
Flap healing was uncomplicated in all cases. Only 6 weeks after surgery, the flap was stable, making it possible to start adjuvant therapy and prosthetic rehabilitation swiftly. The flap is adapted to the near cone-shape of the orbit. The mean (± standard deviation) surface area of the measured orbits is (39.58 ± 3.32) cm2. The territory of the angular artery provides the periosteal flap arterial blood supply. Venous drainage is via venous networks surrounding the artery.

Conclusions:
Use of the pericranial flap makes it possible to close the orbital cavity promptly with minimal donor site defect and a short operating time, thereby minimizing the surgical risk and speeding up physical and psychological recovery.
The Pedicled Anterolateral Thigh Flap for Donor Site Closure after a Large Superficial Circumflex Iliac Artery Perforator Flap Harvest
Authors: Onuma Haruka , Fuse Yuma , Karakawa Ryo , Yano Tomoyuki , Yoshimatsu Hidehiko 
Published: July 2023

Summary:
The superficial circumflex iliac artery perforator (SCIP) flap is useful for covering defects in the extremities because its pedicle size can match many recipient options. However, when harvesting a large flap, skin grafting of the donor site is not highly recommended because of the mobility of the hip joint and occasional lymphorrhea. Here, we present a case of a successful reconstruction of a defect in the lower leg after sarcoma resection, using a large SCIP flap. A 58-year-old man underwent resection of a large soft tissue tumor in the lower leg, resulting in a 16 × 14 cm defect. A 25 × 14 cm SCIP flap was harvested from the groin, and the superficial circumflex iliac artery and the superficial circumflex iliac vein were anastomosed to the saphenous artery and the great saphenous vein, respectively, in an end-to-end fashion. For coverage of the groin donor site, a 25 × 8 cm pedicled anterolateral thigh (ALT) flap was harvested from the ipsilateral lateral thigh and was pulled through a subcutaneous tunnel to the groin. The additional operative time for pedicled ALT flap elevation and transfer was approximately 15 minutes. With this pedicled ALT flap, the donor site of the SCIP flap could be closed directly over a drain. The follow-up at 3 months showed complete survival of both flaps, and the patient was able to walk with a cane. The pedicled ALT flap allows for direct closure of the donor site after a large SCIP flap harvest.
Successful Treatment of Wounds from Nonuremic Calciphylaxis with Acellular Piscine Dermis
Authors: Shahriari Shawhin , Ensign Eric , Huang Samantha , Harrison Joshua , Whisonant Cees , Aubin-Lemay Camille 
Published: July 2023

Summary:
In this report, we present a 57-year-old man with chronic bilateral lower extremity wounds from nonuremic calciphylaxis, which were successfully reconstructed using a piscine-derived acellular dermal matrix. The acellular dermal matrix incorporated quickly, providing a wound bed that was amenable to skin grafting. We demonstrate that this is an effective off-the-shelf solution for these chronic wounds, resulting in pain reduction and complete closure of the wounds, allowing the patient to return to his previous baseline activities, and improving his quality of life.
Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women
Authors: Watz Michel E.S. , Tivesten Åsa , Ottarsdottir Kristin , Li Ying , Hellgren Margareta I. , Lindblad Ulf , Daka Bledar 
Published: July 2023

Objective:
To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension.

Methods:
In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002–2005. A representative sample of 1954 men and women was invited to follow-up in 2012–2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs.

Results:
Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58–0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = −1.5 mmHg, 95% CI − 2.2 to −0.8) and DBP (delta = − 1.0 mmHg, 95% CI − 1.5 to −0.4), after adjusting for covariates.

Conclusion:
SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.
Status of Type II vs. Type I Bipolar Disorder: Systematic Review with Meta-Analyses
Authors: Hernandorena Carolina V. , Baldessarini Ross J. , Tondo Leonardo , Vázquez Gustavo H. 
Published: July 2023

Learning Objectives: After participating in this CME activity, the psychiatrist should be better able to
• Analyze and compare the different bipolar disorder (BD) types.
• Identify markers that distinguish BD types and explain how the DSM-IV defines the disorder.

Abstract
Since the status of type II bipolar disorder (BD2) as a separate and distinct form of bipolar disorder (BD) remains controversial, we reviewed studies that directly compare BD2 to type I bipolar disorder (BD1). Systematic literature searching yielded 36 reports with head-to-head comparisons involving 52,631 BD1 and 37,363 BD2 patients (total N = 89,994) observed for 14.6 years, regarding 21 factors (with 12 reports/factor). BD2 subjects had significantly more additional psychiatric diagnoses, depressions/year, rapid cycling, family psychiatric history, female sex, and antidepressant treatment, but less treatment with lithium or antipsychotics, fewer hospitalizations or psychotic features, and lower unemployment rates than BD1 subjects. However, the diagnostic groups did not differ significantly in education, onset age, marital status, [hypo]manias/year, risk of suicide attempts, substance use disorders, medical comorbidities, or access to psychotherapy. Heterogeneity in reported comparisons of BD2 and BD1 limits the firmness of some observations, but study findings indicate that the BD types differ substantially by several descriptive and clinical measures and that BD2 remains diagnostically stable over many years. We conclude that BD2 requires better clinical recognition and significantly more research aimed at optimizing its treatment.
Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions
Authors: Clapp Averill , Shawber Carrie J. , Wu June K. 
Published: July 2023

Background:
Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations.

Methods:
A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms “venous malformation,” “lymphatic malformation,” “lymphaticovenous malformation,” “genetic variant,” “genetic mutation,” “endothelial cells,” and “animal model.” Relevant publications were reviewed and summarized.

Results:
The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments.

Conclusion:
Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.
Esophageal Lichen Planus
Authors: Aby Elizabeth S. , Eckmann Jason D. , Abimansour Jad , Katzka David A. , Beveridge Claire , Triggs Joseph R. , Dbouk Mohamad , Abdi Tsion , Turner Kevin O. , Antunes Catiele , Zhuo Justin , Kamal Afrin N. , Patel Parth , Gyawali C. Prakash , Sloan Joshua A. 
Published: July 2023

Goals:
To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP).

Background:
ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series.

Study:
A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States.

Results:
Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers.

Conclusions:
Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.
Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution
Authors: Jacob Jake , Millien Valentine , Berger Scott , Hernaez Ruben , Ketwaroo Gyanprakash A. , Flores Avegail G. , Hou Jason K. , Jarbrink-Sehgal Maria E. , Khalaf Natalia I. , Rosen Daniel G. , El-Serag Hashem B. , Tan Mimi C. 
Published: July 2023

Background:
Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital.

Methods:
This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021.

Results:
In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P<0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P<0.001). Because gastric biopsy location was known in 90% of patients (P<0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% (P<0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort.

Conclusions:
GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.
Myositis-associated interstitial lung disease
Authors: Vu Trang T.T. , Brown Kevin K. , Solomon Joshua J. 
Published: July 2023

Purpose of review
In idiopathic inflammatory myopathies (IIMs), interstitial lung disease (ILD) is common and the autoantibody profile, made up of myositis-specific and myositis-associated (MSA and MAA) antibodies, can predict the clinical phenotype and progression over time. This review will focus on the characteristics and management of antisynthetase syndrome related ILD and anti-MDA5 positive ILD, which are the most clinically relevant subtypes.

Recent findings
The prevalence of ILD in IIM has been estimated in Asia, North America and Europe at 50, 23 and 26%, respectively, and is increasing. In antisynthetase syndrome related ILD, the clinical presentation, progression and prognosis varies among anti-ARS antibodies. ILD is more common and severe in patients with anti-PL-7/anti-PL-12 antibodies when compared with anti Jo-1 patients. The prevalence of anti-MDA5 antibodies is higher in Asians (11–60%) than in whites (7–16%). Sixty-six percent of antisynthetase syndrome patients had ‘chronic ILD’ compared with the more rapidly progressive ILD (RP-ILD) seen in 69% of patients with anti-MDA5 antibodies.

Summary
ILD is most common in the antisynthetase subtype of IIM and can be a chronic indolent or RP- ILD. The MSA and MAAs are associated with different clinical phenotypes of ILD. Treatments typically involve combinations of corticosteroids and other immunosuppressants.
Impact of Sleep Disturbance on Fatigue, Nausea, and Pain: Mediating Role of Depressive Symptoms Among Youth With Disorders of Gut-Brain Interaction
Authors: Bedree Helen , Tran Susan T. , Koven Marissa L. , Wershil Sarah J. , Fortunato John E. , Essner Bonnie S. 
Published: July 2023

Objectives:
A high degree of sleep disturbance is reported among youth with disorders of gut-brain interaction (DGBIs). Given that sleep quality impacts a range of pediatric health outcomes including somatic sensations (eg, pain) and depressive mood occurs relatively frequently among youth with DGBIs, there is a dire need to disentangle the unique contributions of sleep and depressive mood on the somatic sensations experienced by youth with DGBIs. We aimed to examine whether depressive mood mediates the relations among sleep disturbance and pain intensity, nausea, and fatigue among youth with DGBIs.

Methods:
One hundred eighteen patients aged 8–17 years (M
age = 14.05, SD = 2.88; 70.34% female), 83.05% White/non-Hispanic recruited at a pediatric neurogastroenterology clinic completed measures of sleep disturbance, nausea, fatigue, pain intensity, and depressive mood. Three mediation models examined the effect of sleep disturbance on nausea, fatigue, and pain, with depressive mood as a mediator.

Results:
Participants reported moderate sleep disturbance. Depressive mood partially mediated the significant, respective relations between greater sleep disturbance and more severe nausea and fatigue. Sleep disturbance was significantly associated with higher pain intensity; however, depressive mood was not a significant mediator of this relation.

Conclusions:
Sleep quality is a major concern among youth with DGBIs. Low sleep quality may worsen nausea and fatigue via co-occurring increases in depressive mood symptoms. In contrast, sleep disturbance may directly increase pain, regardless of youths’ depressive mood symptoms. Future research should explore these relations through prospective studies leveraging a combination of subjective and objective assessment approaches.