bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphoproteomics Reveals the Wolframin-Calcium Axis as an Important Pathogenic Signaling Node in Primary Aldosteronism
Authors: Ma Linqiang , Yang Shumin , Yang Yi , Chen Xiangjun , Yang Jun , He Yifan , Cheng Qingfeng , Li Junlong , Kang Bing , Tang Siying , Zhang Aipin , Shu Xiaoyu , Li Xiaoyu , Shen Hang , Jing Ying , Song Ying , Li Qifu , Hu Jinbo 
Published: February 2023

Background:
Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown.

Methods:
We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line.

Results:

The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411,
P
<0.001). Among 97 APA cases for validation, a higher expression level of wolframin was associated with a higher plasma aldosterone concentration postcaptopril challenge test and a higher systolic blood pressure. In vitro, the secretion of aldosterone was enhanced by wolframin overexpression, while aldosterone secretion in response to potassium or angiotensin II was inhibited by the knockdown of wolframin. Further in vivo and in vitro data demonstrated the wolframin-calcium axis as an important regulator of CYP11B2 expression and aldosterone production.

Conclusions:
Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.
Formal Verification of Deep Brain Stimulation Controllers for Parkinson's Disease Treatment
Authors: Nawaz Arooj , Hasan Osman , Jabeen Shaista 
Published: February 2023

Abstract
Deep brain stimulation (DBS) is a widely accepted treatment for the Parkinson's disease (PD). Traditionally, it is done in an open-loop manner, where stimulation is always ON, irrespective of the patient needs. As a consequence, patients can feel some side effects due to the continuous high-frequency stimulation. Closed-loop DBS can address this problem as it allows adjusting stimulation according to the patient need. The selection of open- or closed-loop DBS and an optimal algorithm for closed-loop DBS are some of the main challenges in DBS controller design, and typically the decision is made through sampling based simulations. In this letter, we used model checking, a formal verification technique used to exhaustively explore the complete state space of a system, for analyzing DBS controllers. We analyze the timed automata of the open-loop and closed-loop DBS controllers in response to the basal ganglia (BG) model. Furthermore, we present a formal verification approach for the closed-loop DBS controllers using timed computation tree logic (TCTL) properties, that is, safety, liveness (the property that under certain conditions, some event will eventually occur), and deadlock freeness. We show that the closed-loop DBS significantly outperforms existing open-loop DBS controllers in terms of energy efficiency. Moreover, we formally analyze the closed-loop DBS for energy efficiency and time behavior with two algorithms, the constant update algorithm and the error prediction update algorithm. Our results demonstrate that the closed-loop DBS running the error prediction update algorithm is efficient in terms of time and energy as compared to the constant update algorithm.
Macroscopic Gamma Oscillation With Bursting Neuron Model Under Stochastic Fluctuation
Authors: Yoshikai Yuto , Zheng Tianyi , Kotani Kiyoshi , Jimbo Yasuhiko 
Published: February 2023

AbstractGamma oscillations are thought to play a role in information processing in the brain. Bursting neurons, which exhibit periodic clusters of spiking activity, are a type of neuron that are thought to contribute largely to gamma oscillations. However, little is known about how the properties of bursting neurons affect the emergence of gamma oscillation, its waveforms, and its synchronized characteristics, especially when subjected to stochastic fluctuations. In this study, we proposed a bursting neuron model that can analyze the bursting ratio and the phase response function. Then we theoretically analyzed the neuronal population dynamics composed of bursting excitatory neurons, mixed with inhibitory neurons. The bifurcation analysis of the equivalent Fokker-Planck equation exhibits three types of gamma oscillations of unimodal firing, bimodal firing in the inhibitory population, and bimodal firing in the excitatory population under different interaction strengths. The analyses of the macroscopic phase response function by the adjoint method of the Fokker-Planck equation revealed that the inhibitory doublet facilitates synchronization of the high-frequency oscillations. When we keep the strength of interactions constant, decreasing the bursting ratio of the individual neurons increases the relative high-gamma component of the populational phase-coupling functions. This also improves the ability of the neuronal population model to synchronize with faster oscillatory input. The analytical frameworks in this study provide insight into nontrivial dynamics of the population of bursting neurons, which further suggest that bursting neurons have an important role in rhythmic activities.
Weather Types and Their Influence on PM10 and O3 Urban Concentrations in the Cergy-Pontoise Conurbation
Authors: Lagmiri Souad , Dahech Salem 
Published: February 2023

Abstract
Daily atmospheric concentrations of the pollutants PM10 and O3 vary according to weather types. This study aims to identify the weather patterns associated with PM10 and O3 pollution episodes from 2009 to 2020. Episodes characterized by exceedance of World Health Organization standards were identified, and their duration and persistence were studied. The results show that air pollution days are associated with three atmospheric patterns for PM10 and four for O3. The dominant weather pattern corresponds to an anticyclonic situation in central and Eastern Europe with a ridge of high pressure over France at the surface and 500-hPa geopotential height. For PM10, the persistent high-concentration sequences were found to be associated with a thermal inversion constraining the vertical dispersion of pollutants. For O3, the four weather types responsible for ozone pollution all have a higher occurrence in summer. The highest percentage (46% of days) is associated with the presence of a ground-level barometric marsh (an area of the atmosphere between two weather systems where the pressure varies slightly but is slightly low) and a ridge at 500 hPa (weather type T1). Similarly, thermal inversions and thermal winds cause pollution to persist beyond 8 consecutive days.

Significance Statement
Air quality is not only influenced by ground-level emissions, but also by complex meteorological processes that can contribute to pollutant accumulations. The importance of this research is that the prediction of these processes helps to prevent the development of extreme concentrations near the surface. The results of this study provide a better understanding of how characteristic weather patterns in the Cergy-Pontoise conurbation impact PM10 and O3 pollutant levels. These impacts are expressed by the intensity and frequency of pollution episodes.
Implantable Shock Absorber Provides Superior Pain Relief and Functional Improvement Compared With High Tibial Osteotomy in Patients with Mild-to-Moderate Medial Knee Osteoarthritis: A 2-Year Report
Authors: Diduch David R. , Crawford Dennis C. , Ranawat Anil S. , Victor Jan , Flanigan David C. 
Published: February 2023

Objective Up to 10 million Americans below the age of 65 years have symptomatic knee osteoarthritis (OA) and may not yet be candidates for arthroplasty. In response, a subcutaneous implantable shock absorber (ISA) that unloads the knee has been developed. The safety and effectiveness of ISA treatment were compared against a surgical unloading control, high tibial osteotomy (HTO). Design This was a prospective open-label cohort study with a historical control arm. Subjects underwent ISA placement or HTO. The primary endpoint was a composite variable combining pain, function, specific adverse events, integrity of implant or hardware, and conversion to subsequent surgery. Pain and function outcomes (Western Ontario and McMaster Universities Arthritis Index scores) were assessed through 24 months. Adverse events were tracked. Results The primary endpoint demonstrated superiority of the ISA arm versus the HTO arm, with 85.6% of ISA subjects meeting all criteria compared with 65.5% of HTO subjects. In addition, all 5 secondary endpoints showed superiority of ISA over HTO. At 24 months, the proportions of subjects considered responders were 95.8% (ISA) versus 87.9% (HTO) for pain and 91.7% (ISA) versus 81.3% (HTO) for function. The ISA procedure was well tolerated, with 13.4 days to full weightbearing status versus 58.0 days for the HTO arm. Conclusions Treatment with an ISA demonstrated noninferiority and superiority versus treatment with HTO in subjects aged 25-65 years who had OA of the medial knee. Treatment with ISA has high clinical benefit and is durable through at least 24 months.
Impact of second primary malignancy post–autologous transplantation on outcomes of multiple myeloma: a CIBMTR analysis
Authors: Ragon Brittany Knick , Shah Mithun Vinod , D’Souza Anita , Estrada-Merly Noel , Gowda Lohith , George Gemlyn , de Lima Marcos , Hashmi Shahrukh , Kharfan-Dabaja Mohamed A. , Majhail Navneet S. , Banerjee Rahul , Saad Ayman , Hildebrandt Gerhard C. , Mian Hira , Abid Muhammad Bilal , Battiwalla Minoo , Lekakis Lazaros J. , Patel Sagar S. , Murthy Hemant S. , Nieto Yago , Strouse Christopher , Badawy Sherif M. , Al Hadidi Samer , Dholaria Bhagirathbhai , Aljurf Mahmoud , Vesole David H. , Lee Cindy H. , Pawarode Attaphol , Gergis Usama , Miller Kevin C. , Holmberg Leona A. , Afrough Aimaz , Solh Melhem , Munshi Pashna N. , Nishihori Taiga , Anderson Larry D. , Wirk Baldeep , Kaur Gurbakhash , Qazilbash Muzaffar H. , Shah Nina , Kumar Shaji K. , Usmani Saad Z. 
Published: February 2023

Abstract
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P &lt; .001 and HR 5.01, P &lt; .001, respectively) and OS (HR 3.85, P &lt; .001 and HR 8.13, P &lt; .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post–auto-HSCT.
BRASD trial: biomechanical reposition techniques in anterior shoulder dislocation—a randomized multicenter clinical trial
Authors: Baden David N. , Roetman Martijn H. , Boeije Tom , Mullaart Nieke , Boden Ralph , Houwert Roderick M. , Heng Marilyn , Groenwold Rolf H. H. , van der Meijden Olivier A. J. 
Published: February 2023

AbstractBackgroundBiomechanical reduction techniques for shoulder dislocations have demonstrated high reduction success rates with a limited pain experience for the patient. We postulated that the combination of biomechanical reduction techniques with the shortest length of stay would also have the lowest pain experience and the highest first reduction success rate.MethodsA randomized multicenter clinical trial was performed to compare different biomechanical reduction techniques in treating anterior shoulder dislocations without the use of invasive pain relief. Patients who were able to perform adduction of the arm were randomly assigned to Cunningham, the modified Milch, and the scapular manipulation technique. Those who were not able to do so were randomly assigned to modified Milch and the scapular manipulation technique. Primary outcomes were emergency department length of stay and pain experienced during the reduction process, measured by the numeric pain rating scale. Secondary outcomes were reduction time, reduction success, use of analgesics or sedatives, and complications.ResultsThree hundred eight patients were included, of whom 134 were in the adduction group. In both groups, no differences in emergency department length of stay and experienced pain were observed between the treatment arms. In the adduction group, the modified Milch technique had the highest first reduction success rates 52% (p = 0.016), within protocol 61% (p = 0.94), and with sedation in the ED 100% ( −). In the no-adduction group, the modified Milch was also the most successful primary reduction technique with 51% success (p = 0.040), within protocol 66% (p = 0.90), and with sedation in the ED 98% (p = 0.93). No complications were recorded in any of the techniques.ConclusionA combination of biomechanical techniques resulted in a similar length of stay in the emergency department and showed similar pain scores with an overall high success rate of reduction. In both groups, the modified Milch had the highest first-reduction success rate.Trial registrationNetherlands Trial Register NTR5839—1 April 2016. Ethical committee Noord-Holland with the CCMO-number NL54173.094.15
The role of high serum triglyceride levels on pancreatic necrosis development and related complications
Authors: Hidalgo Nils Jimmy , Pando Elizabeth , Alberti Piero , Mata Rodrigo , Fernandes Nair , Adell Montse , Villasante Sara , Blanco Laia , Balsells Joaquim , Charco Ramon 
Published: February 2023

Abstract
Background
The relevance of elevated serum triglyceride (TG) levels in the early stages of acute pancreatitis (AP) not induced by hypertriglyceridemia (HTG) remains unclear. Our study aims to determine the role of elevated serum TG levels at admission in developing pancreatic necrosis.

Methods
We analyzed the clinical data collected prospectively from patients with AP. According to TG levels measured in the first 24 h after admission, we stratified patients into four groups: Normal TG (< 150 mg/dL), Borderline-high TG (150–199 mg/dL), High TG (200–499 mg/dL) and Very high TG (≥ 500 mg/dL). We analyzed the association of TG levels and other risk factors with the development of pancreatic necrosis.

Results
A total of 211 patients were included. In the Normal TG group: 122, in Borderline-high TG group: 38, in High TG group: 44, and in Very high TG group: 7. Pancreatic necrosis developed in 29.5% of the patients in the Normal TG group, 26.3% in the Borderline-high TG group, 52.3% in the High TG group, and 85.7% in the Very high TG group. The trend analysis observed a significant association between higher TG levels and pancreatic necrosis (p = 0.001). A multivariable analysis using logistic regression showed that elevated TG levels ≥ 200 mg/dL (High TG and Very high TG groups) were independently associated with pancreatic necrosis (OR: 3.27, 95% CI − 6.27, p < 0.001).

Conclusions
An elevated TG level at admission ≥ 200 mg/dl is independently associated with the development of pancreatic necrosis. The incidence of pancreatic necrosis increases proportionally with the severity of HTG.
A multicenter evaluation of antibacterial use in hospitalized patients through the SARS-Cov-2 pandemic waves
Authors: Puzniak Laura A. , Bauer Karri A. , Yu Kalvin C. , Watts Janet A. , Ai ChinEn , Gupta Vikas 
Published: February 2023

Abstract
Background
Excessive use of antibiotics has been reported during the SARS-CoV-2 pandemic. We evaluated trends in antibiotic use and culture positive Gram-negative (GN)/Gram-positive (GP) pathogens in US hospitalized patients before and during the SARS-CoV-2 pandemic.

Methods
This multicenter, retrospective study included patients from 271 US facilities with > 1-day inpatient admission with discharge or death between July 1, 2019, and October 30, 2021, in the BD Insights Research Database. We evaluated microbiological testing data, antibacterial use, defined as antibacterial use ≥ 24 h in admitted patients, and duration of antibacterial therapy.

Results
Of 5,518,744 patients included in the analysis, 3,729,295 (67.6%) patients were hospitalized during the pandemic with 2,087,774 (56.0%) tested for SARS-CoV-2 and 189,115 (9.1%) testing positive for SARS-CoV-2. During the pre-pandemic period, 36.2% were prescribed antibacterial therapy and 9.3% tested positive for select GN/GP pathogens. During the SARS-CoV-2 pandemic, antibacterial therapy (57.8%) and positive GN/GP culture (11.9%) were highest in SARS-CoV-2-positive patients followed by SARS-CoV-2-negative patients (antibacterial therapy, 40.1%; GN/GP, pathogens 11.0%), and SARS-CoV-2 not tested (antibacterial therapy 30.4%; GN/GP pathogens 7.2%). Multivariate results showed significant decreases in antibacterial therapy and positive GN/GP cultures for both SARS-CoV-2-positive and negative patients during the pandemic, but no significant overall changes from the pre-pandemic period to the pandemic period.

Conclusions
There was a decline in both antibacterial use and positive GN/GP pathogens in patients testing positive for SARS-CoV-2. However, overall antibiotic use was similar prior to and during the pandemic. These data may inform future efforts to optimize antimicrobial stewardship and prescribing.
Phase II randomized, double blind, placebo controlled, clinical trial of safety and immunogenicity of an inactivated SARS-CoV-2 vaccine FAKHRAVAC in adults aged 18–70 years
Authors: Gholami Fatemeh , Hamidi Farahani Ramin , Karimi Rahjerdi Ahmad , Ahi Mohammadreza , Sheidaei Ali , Gohari Kimiya , Rahimi Zahra , Ansarifar Akram , Basiri Pouria , Moradi Milad , Jahangiri Arash , Naderi Kosar , Ghasemi Soheil , Khatami Pezhman , Honari Mohsen , Khodaverdloo Samane , Shooshtari Mohammad , Mehr Azin Hajar , Moradi Sohrab , Shafaghi Batool , Allahyari Hossein , Monazah Arina , Khodaei Poor Ali , Taghva Zahra , Bakhshande Hooman , Karimi Nia Mohammad , Solaymani Dodaran Masoud , Forooghizade Mohsen 
Published: February 2023

Abstract
Background
The FAKHRAVAC®, an inactivated SARS-CoV-2 vaccine, was assessed for safety and immunogenicity in a phase II trial.

Methods
We did a phase II, single-centered, randomized, double-blind, placebo-controlled clinical trial of the FAKHRAVAC inactivated SARS-CoV-2 vaccine on adults aged 18 to 70. The two parallel groups received two intramuscular injections of either a 10-µg vaccine or a placebo at 2-week intervals. The participants' immunogenicity responses and the occurrence of solicited and unsolicited adverse events were compared over the study period of up to 6 months. Immunogenicity outcomes include serum neutralizing antibody activity and specific IgG antibody levels.

Results
Five hundred eligible participants were randomly (1:1) assigned to vaccine or placebo groups. The median age of the participants was 36 years, and 75% were male. The most frequent local adverse reaction was tenderness (21.29% after the first dose and 8.52% after the second dose), and the most frequent systemic adverse reaction was headache (11.24% after the first dose and 8.94% after the second dose). Neutralizing antibody titers two and four weeks after the second injection in the vaccine group showed about 3 and 6 times increase compared to the placebo group (GMR = 2.69, 95% CI 2.32–3.12, N:309) and (GMR = 5.51, 95% CI 3.94–8.35, N:285). A four-fold increase in the neutralizing antibody titer was seen in 69.6% and 73.4% of the participants in the vaccine group two and four weeks after the second dose, respectively. Specific ELIZA antibody response against a combination of S1 and RBD antigens 4 weeks after the second injection increased more than three times in the vaccine compared to the placebo group (GMR = 3.34, 95% CI 2.5–4.47, N:142).

Conclusions
FAKHRAVAC® is safe and induces a significant humoral immune response to the SARS-CoV-2 virus at 10-µg antigen dose in adults aged 18–70. A phase III trial is needed to assess the clinical efficacy.
Trial registration: Trial Registry Number: Ref., IRCT20210206050259N2 (http://irct.ir; registered on 08/06/2021)
Sepsis following acute pyelonephritis caused by Trueperella bernardiae: a case report and literature review
Authors: Matsuhisa Yuki , Kenzaka Tsuneaki , Kobayashi Shinichiro , Taguchi Jun , Hirose Hideo , Gotoh Tadao 
Published: February 2023

Abstract
Background
Trueperella bernardiae is a coryneform, gram-positive bacterium that is a commensal of the skin and upper respiratory tract. It is treated as a contaminant and rarely causes infections. Blood, urine, and abscesses have been previously reported as the most common sites of infection. Infections caused by T. bernardiae are rarely reported in bedridden very old patients with reduced activities of daily living (ADL). In this report, we describe a case of sepsis due to acute pyelonephritis caused by T. bernardiae in a very old patient with impaired ADL.

Case presentation
A 94-year-old woman had a home visit from her local physician. She was bedridden and used diapers. On the day of admission, she presented with fever and dyspnea and was admitted with a diagnosis of sepsis associated with acute pyelonephritis. T. bernardiae was detected in blood and urine cultures; furthermore, multiple bacteria were detected in a urine culture. She was treated with ampicillin/sulbactam 3 g every 12 h on the day of admission. The fever was controlled, and inhaled oxygen 1 L/min via a nasal cannula was administered for dyspnea until hospitalization day 2. On hospitalization day 2, her fever resolved to 36 °C. Antimicrobials were de-escalated and changed to cephazolin and then to cephalexin on hospitalization days 9 and 16, respectively, and were continued until day 22. On hospitalization day 28, the urinary tract infection flared up; however, her fever resolved by hospitalization day 38 after the re-administration of antimicrobial agents. She was discharged on hospitalization day 60.

Conclusions
We encountered a rare case of sepsis following acute pyelonephritis caused by T. bernardiae infection. When bedridden, diaper-using, very old patients present with urinary tract infections caused by multiple bacteria, the presence of rare opportunistic organisms, such as T. bernardiae, should be considered.