bluuebunny/crossref_metadata_2025 huggingface dataset:
Rickets, Vitamin D, and Ca/P Metabolism
Authors: Miller Walter L. , Imel Erik A.
Published: November 2022

Rickets was a major public health problem dating from Roman times, and medical descriptions of rickets date from the 17th century. Sniadecki first advocated treatment by exposure to sunshine in 1822; contemporaneously, several British physicians advocated use of cod liver oil. Both approaches were successful. Work in 1924 showed that exposure to UV light endowed fats and other foods with antirachitic properties. Vitamins D2 and D3, the antirachitic agent in cod liver oil, were, respectively, produced by UV radiation of ergosterol and 7-dehydrocholesterol. Calcitriol (1,25[OH]2D3) was identified as the biologically active form of vitamin D in the early 1970s. The vitamin D 25-hydroxylase, 24-hydroxylase, and 1α-hydroxylase were cloned in the 1990s and their genetic defects were soon delineated. The vitamin D receptor was also cloned and its mutations identified in vitamin D-resistant rickets. Work with parathyroid hormone (PTH) began much later, as the parathyroids were not identified until the late 19th century. In 1925, James B. Collip (of insulin fame) identified PTH by its ability to correct tetany in parathyroidectomized dogs, but only in the 1970s was it clear that only a small fragment of PTH conveyed its activity. Congenital hypoparathyroidism with immune defects was described in 1968, eventually linked to microdeletions in chromosome 22q11.2. X-linked hypophosphatemic rickets was reported in 1957, and genetic linkage analysis identified the causative PHEX gene in 1997. Autosomal dominant hypophosphatemic rickets similarly led to the discovery of FGF23, a phosphate-wasting humoral factor made in bone, in 2000, revolutionizing our understanding of phosphorus metabolism.
Treatment Patterns in Newly Diagnosed Patients with Crohn’s Disease Who Received Biologics Following Diagnosis: A Nationwide, Retrospective, Longitudinal, Observational Study Using a Medical Claims Database in Japan
Authors: Hirai Fumihito , Uda Akihito , Ota Mihoko , Takemura Yukiko , Tanaka Keisuke , Iwakiri Ryuichi
Published: November 2022

Introduction: Crohn’s disease (CD) is a chronic inflammatory condition affecting any part of the gastrointestinal tract. Current therapies involve pharmacological efforts to dampen inflammation. Biologics are recommended for patients with steroid-dependent or steroid-refractory disease; however, little is known about current biologic use in real-world settings in Japan. Methods: This observational, longitudinal, cohort study utilized the Japan Medical Data Center (JMDC) database to analyze claims data of patients who were prescribed ≥1 biologic (adalimumab, infliximab, or ustekinumab) following a new CD diagnosis made between January 2009 and January 2019. We primarily assessed the type of first-line treatment prescribed within 6 months of a patient’s first CD diagnosis. Results: Of the 1,346 eligible patients, the most common prescriptions were 5-aminosalicylic acid (5-ASA) monotherapy (26.8%), 5-ASA plus biologic combination (26.3%), and biologic monotherapy (12.9%). First-line biologics were prescribed within 6 months of initial CD diagnosis in 61.1% of patients, either alone or in combination with other therapies. As an individual first-line treatment, the proportion of patients receiving prescriptions of infliximab was high (66.3%) and steroids, low (1.3%). Patients who had a procedure to inspect the small intestine, such as endoscopy (n = 508), were mostly treated with a nonbiologic therapy (74.8%), whereas those who had not (n = 838), mostly received biologics (alone or in combination, 82.8%) as a first-line treatment. Conclusions: In this study, we discovered the typical treatment pattern of patients with CD who received biologics and are registered in the JMDC database in Japan. Biologics were commonly used in the early phase of CD treatment. Treatment with traditional approaches such as steroids and nutritional therapy with evaluation for small intestine lesions, before turning to the use of biologics, may be prudent for achieving optimal outcomes.
Aligning Dentato-Rubro-Thalamic Tract and Subthalamic Nucleus Targets in a Patient with Comorbid Essential Tremor and Parkinson’s Disease: Case Report
Authors: Boogers Alexandra , Van Bogaert Tine , Peeters Jana , Kilic Ugur , Sunaert Stefan , Vandenberghe Wim , Mc Laughlin Myles , De Vloo Philippe , Nuttin Bart
Published: November 2022

Deep brain stimulation is an established treatment option for both essential tremor (ET) and Parkinson’s disease (PD), although typically targeting different brain structures. Some patients are diagnosed with comorbid ET and PD. Selecting the optimal stimulation target in these patients is challenging. We present a patient with comorbid ET and PD in whom we used bilaterally a single parietal trajectory to align the dentato-rubro-thalamic tract and the subthalamic nucleus. Although parietal trajectories are challenging, we reached satisfactory outcomes for both conditions without complications. Single-electrode deep brain stimulation of the dentato-rubro-thalamic tract and the subthalamic nucleus through a parietal approach may represent a feasible treatment option in this patient group.
Encephalitis or Stroke? A Case Report of Thalamic Stroke in COVID Era
Authors: Damodaran Anandi , Koutaich Rim , Nayak Devdutt , Hamad Imad , Gupta Rajesh , Ibrahim Mohammad
Published: November 2022

Introduction: Since 2019, COVID-19 pneumonia caused by SARS-CoV-2 virus has led to a worldwide pandemic. Since then, various neurological manifestations of COVID-19 pneumonia have been reported. Neurological manifestations include headache, anosmia, seizures, and altered mental status. In some cases, it presents as stroke, encephalitis, and neuropathy. Artery of Percheron (AOP) is a variant in the posterior circulation. Here, a single artery arises from the posterior cerebral artery p1 segment. It supplies bilateral thalamus with or without midbrain. Thrombosis in this artery leads to clinical symptoms like reduced level of consciousness, altered mental status, and memory impairment. Case Report: Here, we present a case who presented with fever and altered sensorium without any focal neurological deficits and without known risk factors for stroke. His COVID-19 PCR was positive. He was initially diagnosed as COVID-19 pneumonia with encephalitis and was started on treatment for the same. His initial CT brain and lumbar puncture were normal. The next day, when MRI brain with and without contrast was done, the thalamic stroke due to AOP infarction was diagnosed and appropriate treatment for stroke was initiated. Discussion: Many patients miss the window for thrombolysis because of variable presentation in clinical symptoms with negative imaging. It is also difficult to assess the time of onset of stroke in this varied presentation. Our patient had fever and cough for 2 days and had altered mental status since the morning of admission. During hospital stay, he developed bilateral third nerve palsy. This case also highlights the importance of detailed evaluation in COVID-19 patients with neurological complaints. This helps to avoid delays in treatment and to improve clinical outcomes. As our knowledge of COVID-19 and its varied neurological manifestations evolve, we need to be prepared for more atypical presentation to facilitate timely interventions.
The History of the Insulin-Like Growth Factor System
Authors: Miller Bradley S. , Rogol Alan D. , Rosenfeld Ron G.
Published: November 2022

The growth hormone (GH)–insulin-like growth factor (IGF) cascade is central to the regulation of growth and metabolism. This article focuses on the history of the components of the IGF system, with an emphasis on the peptide hormones, IGF-I and -II, their cell surface receptors, and the IGF binding proteins (IGFBPs) and IGFBP proteases that regulate the availability of the peptide hormones for interaction with their receptors in relevant target tissues. We describe landmark events in the evolution of the somatomedin hypothesis, including evidence that has become available from experiments at the molecular and cellular levels, whole animal and tissue-specific gene knockouts, studies of cancer epidemiology, identification of prismatic human cases, and short- and long-term clinical trials of IGF-I therapy in humans. In addition, this new evidence has expanded our clinical definition of GH insensitivity (GHI) beyond growth hormone receptor mutations (classic Laron syndrome) to include conditions that cause primary IGF deficiency by impacting post-receptor signal transduction, IGF production, IGF availability to interact with the IGF-I receptor (IGF-1R), and defects in the IGF-1R, itself. We also discuss the clinical aspects of IGFs, from their description as insulin-like activity, to the use of IGF-I in the diagnosis and treatment of GH deficiency, and to the use of recombinant human IGF-I for therapy of children with GHI.
Factors Associated with Potentially Inappropriate Prescribing in Patients on Peritoneal Dialysis
Authors: Stojadinovic Milorad , Zivkovic Zaric Radica , Lausevic Mirjana , Jemcov Tamara , Komadina Ljiljana , Petrovic Dejan , Djuric Petar , Bulatovic Ana , Jankovic Slobodan
Published: November 2022

Introduction: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon. Methods: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression. Results: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing. Conclusion: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.
Association between Anatomical Variations of the Circle of Willis and Covert Vascular Brain Injury in the General Population
Authors: Feng Lu , Zhai Fei-Fei , Li Ming-Li , Zhou Li-Xin , Ni Jun , Yao Ming , Jin Zheng-Yu , Cui Li-Ying , Zhang Shu-Yang , Han Fei , Zhu Yi-Cheng
Published: November 2022

Background and Purpose: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. Methods: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. Results: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004–4.270) and CMB presence (OR = 1.542; 95% CI, 1.012–2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069–3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064–2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346–0.915). Conclusions: COW configuration was significantly related to various covert vascular brain injuries.
COVID-19-Related Death in Patients with Alcohol or Substance Use Disorders
Authors: Pavarin Raimondo Maria , Consonni Dario , Lucchi Fabio , Pandolfi Paolo , Marani Silvia , Palmese Francesco , Domenicali Marco
Published: November 2022

Background: People with substance or alcohol use disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population, but the evidence of COVID-19-related mortality in these patients is unclear. Objectives: The aim of the study was to verify whether patients with AUD and SUD have a higher mortality rate for COVID-19-related mortality compared to the general population. Method: We performed a follow-up study to assess mortality in 2020 in a cohort of patients diagnosed for the first time with AUDs or SUDs at the Public Health Services in the metropolitan area of Bologna (Northern Italy) from 2009 to 2019. Results: SUDs/AUDs patients present an excess mortality with respect to the general population for all causes of death and for COVID-19-related mortality. Conclusions: Our data support the need for prevention strategies in SUDs/AUDs patients such as vaccinations.
Hysterectomy for Non-Prolapsed Uterus in Elderly Patients: Predictors of Prolonged Hospital Stay
Authors: Casarin Jvan , Ghezzi Fabio , Pinelli Ciro , Laganà Antonio Simone , Ambrosoli Andrea , Longo Mariangela , Cromi Antonella
Published: November 2022

Objective: The objective of this study was to investigate surgical outcomes and complications of hysterectomy for benign conditions other than prolapse in elderly patients and to define predictors of prolonged hospitalization. Design: Retrospective analysis of prospectively collected data. Setting: This study was conducted in an academic research center. Patients: We utilized our institution surgical database to identify patients aged 60 years or more (“elderly”) who underwent hysterectomy for benign conditions other than pelvic organ prolapse during a 20-year period (January 2000–December 2019). Methods: Length of stay (LOS) of more than 2 days (90th percentile of LOS) was defined as prolonged hospitalization. Patient demographics, comorbid conditions, and surgical approach (vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), and abdominal hysterectomy (AH)) were identified. Patients treated via LH or VH were also grouped as minimally invasive surgery (MIS). Multivariable logistic regression was used to identify factors associated with prolonged LOS. Results: Overall, 334 patients were included in this study, 262 (78.4%) of whom underwent LH, 42 (12.6%) VH, and 30 (9.0%) AH. Median LOS was 2 days (1–8), and 63 (18.8%) patients required prolonged LOS. Compared to AH, median hospital stay was shorter in MIS group (2 days vs. 3 days, p < 0.001). No admission variables were associated with prolonged LOS. The only independent predictors of prolonged LOS were AH (odds ratio 24.82, 95% CI 4.84–127.16) and operative time (odds ratio for 30 mins increased 11.34, 95% CI 1.63–78.78). Compared to those who underwent VH, patients having LH had a higher rate of concomitant salpingo-oophorectomy (96.6% vs. 61.9%, p < 0.001). Limitations: Retrospective single-center study design, number of patients with prolonged hospitalization, and the setting (tertiary minimally invasive gynecology referral center), which might have reduced the generalizability of our results are the limitations of this study. Conclusions: The abdominal route of hysterectomy was found as the main driver of prolonged hospitalization, reinforcing the benefits of MIS for benign hysterectomy in elderly patients with non-prolapsed uteri; the higher chance of performing concomitant salpingo-oophorectomy supports the laparoscopic approach as the first option for these patients.
Overall Adverse Event Profile of Vadadustat versus Darbepoetin Alfa for the Treatment of Anemia Associated with Chronic Kidney Disease in Phase 3 Trials
Authors: Agarwal Rajiv , Anand Sanjeev , Eckardt Kai-Uwe , Luo Wenli , Parfrey Patrick S. , Sarnak Mark J. , Solinsky Christine M. , Vargo Dennis L. , Winkelmayer Wolfgang C. , Chertow Glenn M.
Published: November 2022

Introduction: Anemia frequently occurs in chronic kidney disease (CKD), is associated with poor quality of life and cardiovascular outcomes, and its treatment represents a considerable economic burden to the healthcare system. Although effective, the current standard of care for the treatment of anemia in chronic kidney disease patients with erythropoiesis-stimulating agents requires chronic/ongoing injections, making the treatment less accessible or desirable to patients not treated by in-center maintenance hemodialysis. Furthermore, safety concerns, including an increased risk of cardiovascular events and mortality, have emerged from their use in studies targeting hemoglobin concentrations in the normal or near-normal range. The orally active hypoxia-inducible factor prolyl hydroxylase inhibitor vadadustat may offer advantages over erythropoiesis-stimulating agents by correcting anemia via pathways activating endogenous erythropoietin production. Methods: To comprehensively analyze the safety profile of vadadustat in patients with dialysis-dependent and non-dialysis-dependent CKD-related anemia, we pooled the safety populations from each of the four trials in the phase 3 clinical program (n = 7,373) and compared the risk of treatment-emergent adverse events (TEAEs) for each treatment arm. Results: In patients randomized to vadadustat versus darbepoetin alfa, rates of TEAEs (88.9% vs. 89.3%), treatment-emergent serious adverse events (58.0% vs. 59.3%), and TEAEs leading to death (16.1% vs. 16.2%) were similar, as were rates of adverse events of special interest, including cardiovascular-, hepatic-, and neoplasm-related adverse events. Discussion/Conclusion: Among patients with CKD-related anemia treated with vadadustat, we observed similar rates of adverse events relative to those treated with darbepoetin alfa.
Abstract 136: Vascular Impairment From Acute Exposure To E-cigarette Aerosol Is Rescued By Inhibition Of The Receptor For Advanced Glycation End Products (RAGE)
Authors: Han Daniel D , Qiu Huiliang , Wang Xiaoyin , Rao Poonam , Navabzadeh Mina , Goyal Natasha , Mohammadi Leila , Springer Matthew L
Published: November 2022

Introduction:
E-cigarette use is known to induce vascular impairment by altering vasomotor and cellular functions of the vascular wall, but the molecular mechanism of e-cigarette-induced vascular impairment is largely unexplored. We investigated whether inhibition of RAGE prevents impairment of vasomotor function from acute e-cigarette exposure

Hypothesis:
Impairment of endothelial vasodilatory function requires the activation of RAGE.

Methods:
Anesthetized rats (n=8/group) were exposed to aerosols from flavorless tank style e-cigarettes with and without freebase nicotine (12 mg/ml) or air in a single session of 10 cycles of pulsatile 5s exposure over 5 minutes. For each exposure condition, groups received either 1 mg/kg of RAGE inhibitor FPS-ZM1 or vehicle i.p. 1 hour before exposure (i.e., total of 6 groups). Femoral artery flow-mediated dilation (FMD) was measured using micro-ultrasound before and after exposure.

Results:
Exposure to e-cigarette aerosol with and without nicotine impaired FMD in vehicle groups (8.3±2.7% pre-exposure vs 4.7±2.4% post-exposure, p=0.01; 9.3±4.6% pre- vs 4.8±2.7% post-, p=0.03, respectively), with no change in air control (9.7±3.2% pre- vs 9.3±3.5% post-, p=0.81). Post-exposure FMD in both aerosol groups with vehicle was lower than that in the air group with vehicle (p=0.01 for each aerosol vs air). However, FPS-ZM1 prevented the FMD impairment by aerosol exposure (with nicotine 9.1±3.5% pre- vs 8.9±2.1% post-, p=0.90; without nicotine 9.5±4.3% pre- vs 7.1±2.0% post-, p=0.17), with no change in air control (7.6±2.7% pre- vs 7.4±3.1% post-, p=0.86). Post-exposure FMD values in both aerosol groups receiving FPS-ZM1 were comparable to the air control (p=0.4 and 0.8, respectively). There were no significant difference in post-exposure FMD in the air groups receiving FPS-ZM1 or vehicle (p>0.99).

Conclusions:
RAGE mediates e-cigarette-induced acute impairment of endothelial vasodilatory function.
Abstract 410: Lipoprotein(a) And Apolipoprotein(a) Inhibit Lysis Of Human Thrombi Formed From Whole Blood Under Conditions Of Flow
Authors: Clark Justin R , Boffa Michael , Koschinsky Marlys L
Published: November 2022

The apolipoprotein(a) (apo(a)) component of Lp(a) is homologous to the proenzyme plasminogen, containing domains which are highly similar to plasminogen kringle (K) 4, followed by sequences that closely resemble the K5 and protease domains of plasminogen. Due to key amino acid substitutions/deletions, the protease (P) domain of apo(a) is catalytically inactive. It has been hypothesized that by competing for binding to fibrin, apo(a) can inhibit plasminogen activation and hence fibrinolysis, thereby leading to a prothrombotic role for Lp(a) in the vasculature. Although previous studies have shown inhibition by apo(a), but not Lp(a), of fibrinolysis in an
ex vivo
clot lysis assay, the ability of Lp(a) to inhibit lysis of clots formed from whole blood under conditions of flow that more closely resemble arterial thrombi
in vivo
has not been assessed. In the current study, whole blood was collected from a human donor with low Lp(a) levels, recalcified, and rotated in a Chandler loop device at 30 rpm for 90 minutes. Blood in the closed loops was supplemented with fluorescently labelled fibrinogen, and 0 or 250 nmol/L of purified plasma-derived Lp(a), 17-kringle (17K) recombinant apo(a) or a 17KΔP apo(a) variant lacking the protease-like domain. Interestingly, this protease-like domain has been shown to mediate lysine-dependent binding of apo(a) to plasminogen. Resultant thrombi were exposed to tPA and clot lysis was measured as release of fluorescent fibrinogen over time in a fluorescent plate reader. The addition of 250 nmol/L Lp(a) significantly decreased clot lysis by up to 15% compared to control (p<0.05). On the other hand, 250 nmol/L 17K apo(a) markedly reduced clot lysis by up to 48% relative to control (p<0.01). 17KΔP apo(a), however, did not affect clot lysis in this system. Our findings show that Lp(a) impedes lysis of human clots formed from whole blood under flow conditions, albeit with a much lower potency than 17K apo(a). Interestingly, our results indicate that the antifibrinolytic effect of apo(a) is dependent on the presence of the inactive protease domain, revealing the importance of the apo(a)-plasminogen interaction. These findings suggest that markedly elevated plasma Lp(a) levels might predispose thrombotic events
in vivo
.
Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes
Authors: Prasad Ram , Floyd Jason L. , Dupont Mariana , Harbour Angela , Adu-Agyeiwaah Yvonne , Asare-Bediako Bright , Chakraborty Dibyendu , Kichler Kara , Rohella Aayush , Li Calzi Sergio , Lammendella Regina , Wright Justin , Boulton Michael E. , Oudit Gavin Y. , Raizada Mohan K. , Stevens Bruce R. , Li Qiuhong , Grant Maria B.
Published: November 2022

Background:

We examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D).

Methods:

T1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II);
Akita
mice were orally administered a
Lactobacillus paracasei
(LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention.
Akita
mice with genetic overexpression of
humanAce2
by small intestine epithelial cells (
Vil-Cre.hAce2KI-Akita
) were similarly examined. After 9 months of T1D, circulatory, enteral, and ocular end points were assessed.

Results:

T1D subjects exhibit elevations in gut-derived circulating immune cells (ILC1 cells) and higher gut leakage markers, which were positively correlated with plasma Ang II and DR severity. The LP-ACE2 prevention cohort and genetic overexpression of intestinal ACE2 preserved barrier integrity, reduced inflammatory response, improved hyperglycemia, and delayed development of DR. Improvements in glucose homeostasis were due to intestinal MasR activation, resulting in a GSK-3β (glycogen synthase kinase-3 beta)/c-Myc (cellular myelocytomatosis oncogene)-mediated decrease in intestinal glucose transporter expression. In the LP-ACE2 intervention cohort, gut barrier integrity was improved and DR reversed, but no improvement in hyperglycemia was observed. These data support that the beneficial effects of LP-ACE2 on DR are due to the action of ACE2, not improved glucose homeostasis.

Conclusions:

Dysregulated systemic and intestinal renin-angiotensin system was associated with worsening gut barrier permeability, gut-derived immune cell activation, systemic inflammation, and progression of DR in human subjects. In
Akita
mice, maintaining intestinal ACE2 expression prevented and reversed DR, emphasizing the multifaceted role of the intestinal renin-angiotensin system in diabetes and DR.
Detrimental Role of PDZ-RhoGEF in Pathological Cardiac Hypertrophy
Authors: Huang Jia , Qu Qingrong , Dai Yuxiang , Ren Daoyuan , Qian Juying , Ge Junbo
Published: November 2022

Background:

Postsynaptic density 95/disk-large/ZO-1 Rho guanine nucleotide exchange factor (PDZ-RhoGEF, PRG) functions as a RhoGEF for activated Gα13 and transmits activation signals to downstream signaling pathways in various pathological processes. Although the prohypertrophic effect of activated Gα13 (guanine nucleotide binding protein alpha 13; a heterotrimeric G protein) is well-established, the role of PDZ-RhoGEF in pathological cardiac hypertrophy is still obscure.

Methods:

Genetically engineered mice and neonatal rat ventricular myocytes were generated to investigate the function of PRG in pathological myocardial hypertrophy. The prohypertrophic stimuli-induced alternations in the morphology and intracellular signaling were measured in myocardium and neonatal rat ventricular myocytes. Furthermore, multiple molecular methodologies were used to identify the precise molecular mechanisms underlying PDZ-RhoGEF function.

Results:

Increased PDZ-RhoGEF expression was documented in both hypertrophied hearts and neonatal rat ventricular myocytes. Upon prohypertrophic stimuli, the PDZ-RhoGEF-deficient hearts displayed alleviated cardiomyocyte enlargement and attenuated collagen deposition with improved cardiac function, whereas the adverse hypertrophic responses in hearts and neonatal rat ventricular myocytes were markedly exaggerated by PDZ-RhoGEF overexpression. Mechanistically, RhoA (ras homolog family member A)-dependent signaling pathways may function as the downstream effectors of PDZ-RhoGEF in hypertrophic remodeling, as confirmed by rescue experiments using a RhoA inhibitor and dominant-negative RhoA. Furthermore, PDZ-RhoGEF is associated with activated Gα13 and contributes to Gα13-mediated activation of RhoA-dependent signaling.

Conclusions:

Our data provide the first evidence that PDZ-RhoGEF promotes pathological cardiac hypertrophy by linking activated Gα13 to RhoA-dependent signaling pathways. Therefore, PDZ-RhoGEF has the potential to be a diagnostic marker or therapeutic target for pathological cardiac hypertrophy.
Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report
Authors: Gumz Michelle L. , Shimbo Daichi , Abdalla Marwah , Balijepalli Ravi C. , Benedict Christian , Chen Yabing , Earnest David J. , Gamble Karen L. , Garrison Scott R. , Gong Ming C. , Hogenesch John B. , Hong Yuling , Ivy Jessica R. , Joe Bina , Laposky Aaron D. , Liang Mingyu , MacLaughlin Eric J. , Martino Tami A. , Pollock David M. , Redline Susan , Rogers Amy , Dan Rudic R. , Schernhammer Eva S. , Stergiou George S. , St-Onge Marie-Pierre , Wang Xiaoling , Wright Jacqueline , Oh Young S.
Published: November 2022

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.
Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee
Authors: Nguyen Thanh N. , Castonguay Alicia C. , Siegler James E. , Nagel Simon , Lansberg Maarten G. , de Havenon Adam , Sheth Sunil A. , Abdalkader Mohamad , Tsai Jenny P. , Albers Gregory W. , Masoud Hesham E. , Jovin Tudor G. , Martins Sheila O. , Nogueira Raul G. , Zaidat Osama O. ,   for the SVIN GAPS Committee
Published: November 2022

Background

Recent clinical trials investigating endovascular therapy in the extended time window have opened new treatment paradigms for patients with late‐presenting large vessel occlusion stroke. The aim of this guideline is to provide up‐to‐date recommendations for the diagnosis, selection, and medical or endovascular treatment of patients with large vessel occlusion presenting in the extended time window.

Methods

The Society of Vascular and Interventional Neurology Guidelines and Practice Standards committee assembled a writing group and recruited interdisciplinary experts to review and evaluate the current literature. Recommendations were assigned by the writing group using the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Class of Recommendation/Level of Evidence algorithm and Society of Vascular and Interventional Neurology Guidelines and Practice Standards guideline format. The final guideline was approved by all members of the writing group, the Guidelines and Practice Standards committee, and the Society of Vascular and Interventional Neurology board of directors.

Results

Literature review yielded 3 high‐quality randomized trials and several observational studies that have been extracted to derive the enclosed summary recommendations. In patients with large vessel occlusion presenting in the 6‐ to 24‐hour window and with clinical–imaging mismatch as defined by the DAWN (Diffusion‐Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake‐Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) studies, endovascular therapy is recommended. Noncontrast computed tomography can be used to evaluate infarct size as the sole imaging modality for patient selection, particularly when access to computed tomography perfusion or magnetic resonance imaging is limited or if their performance would incur substantial delay to treatment. In addition, several clinical questions were reviewed based on the available evidence and consensus grading.

Conclusions

These guidelines provide practical recommendations based on recent evidence on the diagnosis, selection, and treatment of patients with large vessel occlusion stroke presenting in the extended time window.
A reviewof the application of canopy bridges in the conservation of primates and other arboreal animals across Brazil
Authors: Zimmermann Teixeira Fernanda , Gonçalves da Silva Lucas , Abra Fernanda , Rosa Clarissa , Buss Gerson , Guerreiro Marcello , Costa Edson Rodrigues , de Menezes Medeiros Aline Souza , Gordo Marcelo , Secco Helio
Published: November 2022

Brazil is known as a high biodiversity country, but at the same time, it has an extensive road network that threatens its wildlife and ecosystems. The impacts of roads and railways on vertebrates have been documented extensively, and the discussion concerning the implementation of mitigation measures for terrestrial wildlife has increased in the last decade. Arboreal animals are especially affected by the direct loss of individuals due to animal-vehicle collisions and by the barrier effect, because most arboreal species, especially the strictly arboreal ones, avoid going down to the ground to move across the landscape. Here we summarize and review information on existing canopy bridges across Brazil, considering artificial and natural canopy bridge initiatives implemented mainly on road and railway projects. A total of 151 canopy bridges were identified across the country, 112 of which are human-made structures of different materials, while the remaining 39 are natural canopy bridges. We found canopy bridges in three of the six biomes, with higher numbers in the Atlantic Forest and Amazon, the most forested biomes. Most of the canopy bridges are in protected areas (76%) and primates are the most common target taxa for canopy bridge implementation. Our study is the first biogeographic mapping and review of canopy bridges for arboreal wildlife conservation in a megadiverse country. We synthesize the available knowledge concerning canopy bridges in Brazil and highlight gaps that should be addressed by future research and monitoring projects.
Population dynamics of mite species on poplar trees in the Black Sea region of Turkey
Authors: BAS HUSEYIN , OZMAN-SULLIVAN SEBAHAT K. , UECKERMANN EDWARD A. , CHETVERIKOV PHILIPP E. , DOKER ISMAIL
Published: November 2022

The enormous number of mite species across the world includes economically important pests of agricultural plants and forest trees and biological control agents. However, knowledge of their biology and ecology is greatly lacking. Poplar (Populus spp.) is grown in many countries and a number of mite species have previously been recorded. This study was conducted to determine the population dynamics of mites on poplar in 2021 in Samsun Province, Turkey where it is widely grown in plantations, along property boundaries and as a landscape tree.
Evaluation of prey stage preference of the phytoseiid predator, Neoseiulus longispinosus (Evans) to the spider mite pest, Tetranychus macfarlanei Baker and Pritchard (Acari: Tetranychidae)
Authors: JYOTHIS DEVASIA , RAMANI NERAVATHU
Published: November 2022

Tetranychus macfarlanei Baker and Pritchard is considered as a major spider mite pest infesting various agricultural crops across the globe. It is a highly polyphagous species, inducing heavy yield loss annually, thereby affecting the agriculture sector drastically. As an eco-friendly pest management strategy, biological control using phytoseiid predators is gaining significant attention all over the world during the past few decades. Evaluation of predatory potential and prey stage preference provides valuable information on the efficacy of the predatory species in controlling the pest population. Considering this, a comparative evaluation of the feeding preference of a phytoseiid predator, Neoseiulus longispinosus (Evans), was made on different life stages of T. macfarlanei under laboratory conditions of 30±20C and 70±5% RH. The experimental arena used for the feeding experiments consisted of mulberry leaf discs (2 cm2) uniformly arranged over 2% semi-solidified agarose medium placed inside a glass Petri dish. The results revealed that the feeding preference of the adult predator towards the prey stages after 24 hours of experiment followed a decreasing sequence of egg (68%)> nymph (13.3%)> larva (6.6%). The predator nymph also followed a similar order of preference with respective consumption rates of 22%, 6.6% and 6.6% on the egg, larva and nymph of the prey mite, indicating that both the nymphs and the adult females of the predator displayed a significant preference to feed on the eggs of T. macfarlanei. Both predatory life stages showed no preference to the adult females of T. macfarlanei. Statistical analysis using ANOVA revealed a significant variation (p < 0.05) in the feeding preference of the predatory life stages towards the varied prey stages. Thus, the results of the study clearly showed the bio-control potential of N. longispinosus against T. macfarlanei.
Development, reproduction and thermotolerance evaluation of high temperature adapted stain of Neoseiulus barkeri under no selective pressure
Authors: CHU WENQIANG , CHEN HAITAO , GENG LINA , CHEN YIYIN , LI XUANLIANG , JIANG WENJIE , LI YAYING , LIU HUAI
Published: November 2022

Neoseiulus barkeri is a generalist biological control agent of multiple insect pests (Hao et al., 2021). Its development, reproduction and predation ability were negatively affected by short-term heat treatment (Li et al., 2021), further affecting its biocontrol efficiency. We established a high-temperature adapted strain (HTAS) of N. barkeri through long-term heat hardening and acclimation. However, whether the temperature tolerance of HTAS of N. barkeri will change when the selective pressure is removed remains unknown.
Tanytarsini (Diptera: Chironomidae) collected during Polish expeditions to North Korea
Authors: GIŁKA WOJCIECH , GADAWSKI PIOTR
Published: November 2022

This systematic review of non-biting midges of the tribe Tanytarsini is based on materials collected during Polish scientific expeditions to North Korea. Stempellina radoszkowskii sp. nov. is described. Brief illustrated redescriptions of adult males of further eight species, for the first time recorded from North Korea, are presented: Cladotanytarsus (Cladotanytarsus) sinjongensis Ree et Kim, 1988, Micropsectra joganplumosa Sasa et Okazawa, 1991, M. jokatertia Sasa et Ogata, 1999, Tanytarsus iriolemeus Sasa et Suzuki, 2000, T. oyamai Sasa, 1979, T. takahashii Kawai et Sasa, 1985, T. tamadecimus Sasa, 1980 and T. tamaundecimus Sasa, 1980. New synonyms are proposed: Micropsectra tonewdeea Sasa et Tanaka, 2002, syn. nov. [=Micropsectra atrofasciata (Kieffer, 1911)]; Micropsectra tusimalemea Sasa et Suzuki, 1999, syn. nov., M. tusimamenea Sasa et Suzuki, 1999, syn. nov., M. tusimaquerea Sasa et Suzuki, 1999, syn. nov. [=Micropsectra joganplumosa Sasa et Okazawa, 1991], and several further synonyms of the species reviewed are suggested. An annotated checklist of Tanytarsini so far reported from North Korea is given. A historical note on Polish scientific expeditions to Korea is also included.
Review of Kamimuria (Plecoptera: Perlidae) from Zhejiang and Fujian provinces, China, with notes on the morphological variability of K. tienmushanensis Wu, 1938
Authors: HUO QING-BO , XIANG YA-NAN , REHMAN ABDUR , DU YU-ZHOU , ZHU BIN-QING , MURÁNYI DÁVID
Published: November 2022

Two poorly known species of Kamimuria Klapálek, 1907, K. simplex (Chu, 1929) and K. tienmushanensis Wu, 1938, are redescribed and newly recorded for Mt. Wuyi, Fujian. Kamimuria cheni Wu, 1948 and K. crassispina Wu, 1948 are removed from the species list of Fujian. The morphological variability of K. tienmushanensis from different locations is also discussed in this paper.
Engaging with Everyday Sounds
Authors: Cobussen Marcel
Published: November 2022

'Engaging With Everyday Sounds' is a rich and inspiring exploration of the role of sounds in everyday life, including their impact on human actions, emotions, and imagination. Marcel Cobussen intertwines sonic studies with philosophy, sound art, sociology and more to create an impressively lucid and innovative guide to sonic materialism, calling for a re-sensitization to our acoustic environment and arguing that everyday sounds have (micro)political, social, and ethical impact to which we should attend.

Exploring the intellectual history of sound studies as well as local, global, and temporal sonic geographies, Cobussen weaves audio files, images, and journal excerpts into his work to create a multimodal monograph that explores the relationships of humans, nonhumans, and their environments through sound. This accessible and interdisciplinary collection of short, powerful essays will be valuable reading for both academics and the general reader interested in sound studies, sound art, philosophy, or the sociology of everyday life—and for anyone keen to think about the sonic in new and engaging ways.
1 Introduction
Authors: Cobussen Marcel
Published: November 2022

This chapter presents the volume’s purpose of providing a multimedia account of a ‘listening journey’ that the author has undertaken over the course of a year in order to gain more insight into everyday sounds, how we affect them, and how they―in turn―affect us. It emphasizes the importance of conceiving of everyday sounds as worthy of our attention, care, and receptivity, so that we can enact new patterns of engagement with these sounds.

We then turn to the first ‘diary entry’ recording the beginning of the author’s listening journey, with its accompanying audio file. Here, the author sets out further reasoning for questioning the everyday and finding the unfamiliar in the familiar.
Carefully Choose the Baseline: Lessons Learned from Applying XAI Attribution Methods for Regression Tasks in Geoscience
Authors: Mamalakis Antonios , Barnes Elizabeth A. , Ebert-Uphoff Imme
Published: November 2022

Methods of explainable artificial intelligence (XAI) are used in geoscientific applications to gain insights into the decision-making strategy of neural networks (NNs), highlighting which features in the input contribute the most to a NN prediction. Here, we discuss our “lesson learned” that the task of attributing a prediction to the input does not have a single solution. Instead, the attribution results depend greatly on the considered baseline that the XAI method utilizes—a fact that has been overlooked in the geoscientific literature. The baseline is a reference point to which the prediction is compared so that the prediction can be understood. This baseline can be chosen by the user or is set by construction in the method’s algorithm—often without the user being aware of that choice. We highlight that different baselines can lead to different insights for different science questions and, thus, should be chosen accordingly. To illustrate the impact of the baseline, we use a large ensemble of historical and future climate simulations forced with the shared socioeconomic pathway 3-7.0 (SSP3-7.0) scenario and train a fully connected NN to predict the ensemble- and global-mean temperature (i.e., the forced global warming signal) given an annual temperature map from an individual ensemble member. We then use various XAI methods and different baselines to attribute the network predictions to the input. We show that attributions differ substantially when considering different baselines, because they correspond to answering different science questions. We conclude by discussing important implications and considerations about the use of baselines in XAI research.

Significance Statement

In recent years, methods of explainable artificial intelligence (XAI) have found great application in geoscientific applications, because they can be used to attribute the predictions of neural networks (NNs) to the input and interpret them physically. Here, we highlight that the attributions—and the physical interpretation—depend greatly on the choice of the baseline—a fact that has been overlooked in the geoscientific literature. We illustrate this dependence for a specific climate task, in which a NN is trained to predict the ensemble- and global-mean temperature (i.e., the forced global warming signal) given an annual temperature map from an individual ensemble member. We show that attributions differ substantially when considering different baselines, because they correspond to answering different science questions.
Influence of Spatial Dipole Pattern in Asian Aerosol Changes on East Asian Summer Monsoon
Authors: Liu Chao , Yang Yang , Wang Hailong , Ren Lili , Wei Jiangfeng , Wang Pinya , Liao Hong
Published: November 2022

Since China implemented the Air Pollution Prevention and Control Action Plan in 2013, the aerosol emissions in East Asia have been greatly reduced, while emissions in South Asia have continued to increase. This has led to a dipole pattern of aerosol emissions between South Asia and East Asia. Here, the East Asian summer monsoon (EASM) responses to the dipole changes in aerosol emissions during 2013–17 are investigated using the atmosphere model of Community Earth System Model version 2 (CESM2). We show that decreases in East Asian emissions alone lead to a positive aerosol effective radiative forcing (ERF) of 1.59 (±0.97) W m−2 over central-eastern China (25°–40°N, 105°–122.5°E), along with a 0.09 (±0.07)°C warming in summer during 2013–17. The warming intensified the land–sea thermal contrast and increased the rainfall by 0.32 (±0.16) mm day−1. When considering both the emission reductions in East Asia and increases in South Asia, the ERF is increased to 3.39 (±0.89) W m−2, along with an enhanced warming of 0.20 (±0.08)°C over central-eastern China, while the rainfall insignificant decreased by 0.07 (±0.16) mm day−1. It is due to the westward shift of the strengthened western Pacific subtropical high, linked to the increase in black carbon in South Asia. Based on multiple EASM indices, the reductions in aerosol emissions from East Asia alone increased the EASM strength by almost 5%. Considering the effect of the westward shift of WPSH, the dipole changes in emissions together increased the EASM by 5%–15% during 2013–17, revealing an important role of South Asian aerosols in changing the East Asian climate.