bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the FSGS disease gene product and nuclear pore protein NUP205 in regulating nuclear localization and activity of transcriptional regulators YAP and TAZ
Authors: Ester Lioba , Cabrita Inês , Ventzke Michel , Kieckhöfer Emilia , Christodoulou Marita , Mandel Amrei M , Diefenhardt Paul , Fabretti Francesca , Benzing Thomas , Habbig Sandra , Schermer Bernhard 
Published: August 2023

Abstract
Mutations in genes encoding nuclear pore proteins (NUPs) lead to the development of steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FSGS). However, the precise molecular mechanisms by which NUP dysfunction contributes to podocyte injury preceding FSGS remain unclear. The tightly regulated activity of Yes-associated protein (YAP) and WW-domain-containing transcription regulator 1 (TAZ), the transcriptional effectors of the Hippo pathway, is crucial for podocytes and the maintenance of the glomerular filter. In this study, we investigate the impact of NUPs on the regulation of YAP/TAZ nuclear import and activity in podocytes. In unbiased interactome studies using quantitative label-free mass spectrometry, we identify the FSGS disease gene products NUP107, NUP133, NUP205, and Exportin-5 (XPO5) as components of YAP and TAZ protein complexes in podocytes. Moreover, we demonstrate that NUP205 is essential for YAP/TAZ nuclear import. Consistently, both the nuclear interaction of YAP/TAZ with TEA domain transcription factor 1 and their transcriptional activity were dependent on NUP205 expression. Additionally, we elucidate a regulatory feedback mechanism whereby YAP activity is modulated in response to TAZ-mediated NUP205 expression. In conclusion, this study establishes a connection between the FSGS disease protein NUP205 and the activity of the transcriptional regulators and Hippo effectors YAP and TAZ and it proposes a potential pathological role of YAP/TAZ dysregulation in podocytes of patients with pathogenic NUP205 variants.
Calculating a Land Carbon Accounting Factor in the United States: an Example and Implications
Authors: Prisley Stephen P , Sonne Hall Edie 
Published: August 2023

AbstractCompanies that produce and use wood for products and energy find it increasingly important to communicate the carbon balance and potential climate effects of these activities. Computing forest carbon stocks and stock changes, and emissions from operations, are often part of institutional reporting for environmental, social, and governance purposes. This article describes an example methodology to assess forest carbon changes associated with the harvesting of wood products and proposes metrics that could be used to allocate harvesting effects to individual organizations for their reporting purposes. We discuss boundaries (types of forests and carbon pools to include), spatially appropriate evaluations given uncertainty, temporal considerations, risk of reversals, and allocation of net sequestration to products sourced from the region. We also discuss the complex nature of the biogenic carbon cycle and warn about the appropriate interpretation of this methodology.
Reconstruction of cervico-thoracic defect with bipedicled deep inferior epigastric perforator free flap following resection of a giant recurrent thyroid tumor: a case report and review of literature
Authors: Zavala Abraham , Vargas María I , Ayala Walter , Muñoz Antonio , Chávez Miguel A , López Jesús , Delgado Ricardo 
Published: August 2023

Abstract
The bipedicled Deep Inferior Epigastric Perforator (DIEP) flap, originally described and primarily utilized in autologous breast reconstruction for specific cases, has expanded its applications to encompass diverse anatomical regions in recent years. This report presents the case of a 69-year-old woman with a recurrent giant thyroid tumor who underwent surgical resection, resulting in a large cervico-thoracic defect effectively reconstructed using a bipedicled DIEP flap. The patient’s postoperative recovery was uneventful, and the follow-up assessments revealed a healthy, well-perfused flap that provided sufficient coverage to critical structures, adequate restoration of the region contour, and enough volume to offset potential adverse effects of subsequent radiation therapy. In addition, this report incorporates a concise literature review highlighting the expanding indications of the bipedicled DIEP flap beyond breast reconstruction, showing the versatility and efficacy of the bipedicled DIEP flap in addressing complex soft-tissue defects in various anatomical areas.
Two Times Versus Four Times Daily Cephalexin Dosing for the Treatment of Uncomplicated Urinary Tract Infections in Females
Authors: Yetsko Aidan , Draper Heather M , Eid Kristen , Jameson Andrew P , Dumkow Lisa E 
Published: August 2023

Abstract

Background
The current treatment guidelines of the Infectious Diseases Society of America recommend β-lactam antibiotics as alternative rather than first-line agents for the treatment of uncomplicated urinary tract infection (uUTI). Cephalexin is a commonly prescribed first-generation cephalosporin with excellent bioavailability and urinary penetration; however, little data exist to support optimal dosing for uUTI.

Methods
This retrospective multicenter cohort study included adult female patients who received 5 to 7 days of cephalexin for symptomatic uUTI with a cefazolin-susceptible urine culture. The primary objective was to compare uUTI treatment failure (eg, continued or recurrent symptoms within 30 days) between patients treated with cephalexin 500 mg twice daily (BID group) and 500 mg 4 times daily (QID group) in the outpatient setting. Secondary outcomes included time to treatment failure, reported adverse events within 7 days of treatment, and occurrence of Clostridioides difficile within 30 days of treatment.

Results
A total of 261 patients were included (BID, n = 173; QID, n = 88). Baseline characteristics were similar between the groups. Escherichia coli was the most commonly isolated pathogen (85.4%). There was no difference in treatment failure observed between the groups (BID 12.7% vs QID 17%, P = .343), including failure while undergoing therapy (BID 2.3% vs QID 5.7%, P = .438) or recurrence within 30 days (BID 10.4% vs QID 11.3%, P = .438). No differences in reported adverse events (BID 4.6% vs QID 5.6%, P = .103) were observed between groups.

Conclusions
Twice-daily cephalexin is as effective as 4-times-daily dosing for uUTI. A twice-daily dosing strategy may improve patient adherence.
Nuclear protein‐1 is the common link for pathways activated by aging and obesity in chondrocytes: A potential therapeutic target for osteoarthritis
Authors: Tan Li , Armstrong Alexandra R. , Rosas Samuel , Patel Chirayu M. , Vander Wiele Sabrina S. , Willey Jeffrey S. , Carlson Cathy S. , Yammani Raghunatha R. 
Published: August 2023

AbstractPathways leading to osteoarthritis (OA) are diverse depending on the risk factors involved; thus, developing OA therapeutics has been challenging. Here we report that nuclear protein‐1 (Nupr1), a stress‐inducible protein/transcription factor, is activated by pathways associated with obesity and aging in chondrocytes. Treatment of human chondrocytes with free fatty acids (palmitate and oleate; a model for high‐fat diet/obesity) induced PERK signaling and increased expression of caspase‐3, TRB3, and Nupr1. On the other hand, treatment of chondrocytes with menadione (oxidative stress inducer) induced oxidation of IRE1, activated antioxidant response (higher Nrf2 expression), and increased expression of Nupr1 and matrix metalloproteinases. Experimental OA was induced by destabilization of the medial meniscus (DMM) in the knee joints of Nupr1+/+ and Nupr1−/− mice. Loss of Nupr1 expression reduced the severity of cartilage lesions in this model. Together, our findings suggest that Nupr1 is a common factor activated by signaling pathways activated by obesity (ER stress) and age (oxidative stress) and a potential drug target for OA resulting from various risk factors.
Real-world Evidence for Impact of Opioid Agonist Therapy on Nonfatal Overdose in Patients with Opioid Use Disorder during the COVID-19 Pandemic
Authors: Lee Kenneth , Zhao Yue , Merali Tazmin , Fraser Christopher , Kozicky Jan-Marie , Mormont Marie-Christine , Conway Brian 
Published: August 2023

Objectives
The primary objectives of this study were to describe the demographics and clinical characteristics of patients who were treated with buprenorphine extended-release versus buprenorphine-naloxone sublingual tablets versus methadone in a real-world setting and to evaluate the difference in nonfatal overdose events between treatment cohorts.

Methods
This study was a retrospective chart review of patients with opioid use disorder initiating opioid agonist therapy in Canada during the outset of the COVID-19 pandemic (March 11, 2020 to October 31, 2021). Three treatment cohorts were defined by the initial prescribed opioid agonist therapy regimen: buprenorphine extended-release, buprenorphine-naloxone sublingual tablets, and methadone. Baseline characteristics, as well as treatment status, overdose events, and substance use 6 months after treatment initiation were collected using a standardized form.

Results
Nine clinics provided data on 379 patient cases. The incidence rate (number of events per 100 person-years) for a self-reported nonfatal overdose was 46.8 (n = 18), 19.3 (n = 10), and 1.7 (n = 1) in the methadone, buprenorphine-naloxone sublingual tablets, and buprenorphine extended-release cohorts, respectively. The risk-adjusted difference for the proportion of patients with nonfatal overdose was 8.59% (95% confidence interval, 3.10–14.08%; P = 0.0022) for methadone versus buprenorphine extended-release and 6.51% (95% confidence interval, 1.46–11.56%; P = 0.0115) for buprenorphine-naloxone sublingual tablets versus buprenorphine extended-release.

Conclusions
Buprenorphine extended-release was associated with lower rates of nonfatal overdose events compared with daily opioid agonist therapy. Given the limitations of this naturalistic, retrospective design, further prospective studies are needed to validate these findings and demonstrate the potential for long-acting opioid agonist therapy in addressing the opioid crisis.
Early Women Pioneers and the Evolution of Women in Plastic Surgery
Authors: Koljonen Jessie L. , Petro Jane A. , Sommer Nicole Z. 
Published: August 2023

Summary:
The history of women in surgery has been documented since ancient times. Despite this, women physicians have historically encountered unique obstacles in achieving the same respect and privileges as their male counterparts. Early female physicians overcame many challenges to complete their training following graduation from medical school. The first woman in the field of plastic surgery in the United States was Dr. Alma Dea Morani, who became a member of the American Society of Plastic and Reconstructive Surgeons (ASPRS, now ASPS) in 1948. She applied for plastic surgery training six different times over 6 years, until she was accepted at a position where she had shadowing-only privileges. Yet, her steadfast determination and perseverance led her to build a successful career, becoming a role model and advocate for women in plastic surgery. The Women Plastic Surgeons Forum within ASPRS was officially established in 1992; however, informal events began as early as 1979. This group fostered mentorship among emerging female leaders, allowing women to take on leadership roles within national plastic surgery organizations. These women, in turn, have become role models for subsequent generations of women in this field. Plastic surgery has historically seen a higher percentage of female residents relative to other surgical specialties. Studies have shown that female role models are the most influential factor for female medical students interested in plastic surgery, a powerful fact considering women now comprise over 50% of graduating medical students. Female mentorship is essential in fostering the future generation of female plastic surgeons.
Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernia with severe gastroesophageal reflux disease. A retrospective cohort study.
Authors: Habeeb Tamer.A.A.M. , Hussain Abdulzahra , Podda Mauro , Aiolfi Alberto , Kryvoruchko Igor A. , Kalmoush Abd-Elfattah , labib Mohamed fathy , Mustafa Fawzy M , Elbelkasi Hamdi , Hamdy Ahmed , Abo Alsaad Mohamed Ibrahim , Sallam Ahmed M. , Zaitoun Mohamed Abdallah , negm Mohamed , Mostafa Abdelshafy , Abdou Yassin Mahmoud , Elshahidy Tamer Mohamed , abdelmonem elsayed Ashraf , Mansour Mohamed Ibrahim , Elaidy Mostafa.M. , Moursi Adel Mahmoud , yehia Ahmed m , Ashour Hassan , Metwalli Abd-Elrahman M. , abdelhady Waleed A. , Abdelghani Amr , AbdAllah Ehab shehata , Ramadan Alaaedin , Rushdy Tamer 
Published: August 2023

Background:
Laparoscopic Nissen Fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (> 5 cm) with severe GERD (DeMeester score >100).

Materials and Methods:
This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery.

Results:
360 patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9% vs. 8.3%) and recurrent regurgitation (2.2% vs. 5%) showed a lower incidence in the LNF+ group (P=0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0% vs. 3.3% and 0% vs. 2.8% cases in the LNF+ and LNF groups, respectively (P=0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75% vs. 5.6% and 0% vs. 3.9% of patients (P=0.001). Score III postoperative persistent dysphagia was 0% vs. 2.8% in the two groups (P=0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3% vs. 86.7% in both cohorts, respectively (P=0.05).

Conclusions:
Intraoperative high-resolution manometry (HRM) and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint.
Buddi-Chiari syndrome associated with hypereosinophilic syndrome: A case report
Authors: Li Zhaoxia , Li Nan , Ji Zhuhui , Shi Jiahe , Xin Guijie 
Published: August 2023

Rationale:
Budd-Chiari Syndrome (BCS) is a relatively rare clinical disorder with a wide range of symptoms, caused by the obstruction of the hepatic venous outflow. The etiology and pathogenesis of BCS vary in different countries and regions. In Western countries, hepatic venous obstruction is the most common type, and its main cause is closely related to the hypercoagulable state of the body. Inferior vena cava obstruction is common in Asia, and its etiology progresses slowly due to the lack of epidemiological data. [3] Here, we report a rare case of BCS associated with the hypereosinophilic syndrome and discuss the possible causal relationship between the two.

Patient concerns:
The patient was a 33-year-old female with intermittent epistaxis, gum bleeding, and excessive menstrual flow for the past 6 months. The routine blood tests showed elevated levels of eosinophils, and the liver function test showed mildly elevated levels of γ-glutamyl transpeptidase and alkaline phosphatase, and abdominal ultrasound showed hepatosplenomegaly and suspicion of intrahepatic arteriovenous or arteriovenous-portal fistula.

Diagnoses:
Finally, through the improvement of bone marrow aspiration, digital subtraction angiography and gene detection, the diagnosis of BCS combined with hypereosinophilic syndrome was confirmed, and JAK2V617F mutation was highly associated with it.

Interventions:
The patient received endovascular stent implantation and regular oral rivaroxaban anticoagulation therapy after operation.

Outcomes:
Seven months later, enhanced computed tomography (CT) of the hepatobiliary showed that the hepatic bruise-like changes were significantly reduced compared with before, and the right hepatic vein and the right perihepatic vein stent were left in place with a good filling of contrast in the stent.

Lessons:
The patient, in this case, was finally diagnosed with BCS combined with hypereosinophilic syndrome, and to our knowledge, such case reports are rare. Our case report suggest an association between BCS and hypereosinophilic syndrome, but relevant studies are minimal, we hope to conduct larger and higher quality studies on these patients in the future, to provide new directions and basis for the etiology and pathogenesis of these diseases, as well as provide new targets and ideas for clinical treatment.
Exploring potential network pharmacology-and molecular docking-based mechanism of melittin in treating rheumatoid arthritis
Authors: Yang Linfu , Zhao Wenzheng , Gong Xueyang , Yue Dan , Liu Yiqiu , Tian Yakai , Dong Kun 
Published: August 2023

Background:
Rheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people’s living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear.

Methods:
Potential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology.

Results:
In total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products–RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins.

Conclusion:
RA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.
Using emergency department triage for machine learning-based admission and mortality prediction
Authors: Tschoellitsch Thomas , Seidl Philipp , Böck Carl , Maletzky Alexander , Moser Philipp , Thumfart Stefan , Giretzlehner Michael , Hochreiter Sepp , Meier Jens 
Published: August 2023

Aims
Patient admission is a decision relying on sparsely available data. This study aims to provide prediction models for discharge versus admission for ward observation or intensive care, and 30 day-mortality for patients triaged with the Manchester Triage System.

Methods
This is a single-centre, observational, retrospective cohort study from data within ten minutes of patient presentation at the interdisciplinary emergency department of the Kepler University Hospital, Linz, Austria. We trained machine learning models including Random Forests and Neural Networks individually to predict discharge versus ward observation or intensive care admission, and 30 day-mortality. For analysis of the features’ relevance, we used permutation feature importance.

Results
A total of 58323 adult patients between 1 December 2015 and 31 August 2020 were included. Neural Networks and Random Forests predicted admission to ward observation with an AUC-ROC of 0.842 ± 0.00 with the most important features being age and chief complaint. For admission to intensive care, the models had an AUC-ROC of 0.819 ± 0.002 with the most important features being the Manchester Triage category and heart rate, and for the outcome 30 day-mortality an AUC-ROC of 0.925 ± 0.001. The most important features for the prediction of 30 day-mortality were age and general ward admission.

Conclusion
Machine learning can provide prediction on discharge versus admission to general wards and intensive care and inform about risk on 30 day-mortality for patients in the emergency department.
Male infertility with muscle weakness: a point of view
Authors: Khalayli Naram , Achmeh Bassel , Ali Khalil , Aziz Aghiad , Kudsi Maysoun 
Published: August 2023

Introduction and importance:
The most common causes of infertility are idiopathic spermatogenetic disorders, occurring in multiple reproductive or systemic diseases. The underlying genetic disorders influence the treatment and transmission of the disease to the offspring.

Case presentation:
A 32-year-old Syrian male, married for 6 years, presented with primary infertility. The patient had a history of muscle dystrophy for 12 years. He had no previous medical or drug addiction or family history. He had gynecomastia. Semen analysis revealed oligospermia in the patient. Follicle-stimulating hormone was elevated. Gene analysis could not be done due to funding issues. The percutaneous testicular biopsy revealed hypospermatogenesis, atrophy, and marked hyalinization of the seminiferous tubules. Electromyography of the upper extremities demonstrated myotonic discharges, with a waxing–waning frequency, amplitude, and a characteristic ‘engine revving’ sound.

Clinical discussion:
Myotonic dystrophy (MD) is an autosomal dominant inheritance disease with adult onset. Muscle weakness is the predominant presenting feature, with early involvement of the distal limbs and neck muscles and a characteristic facial appearance.
Systemic clinical manifestations may include cardiac conduction defects, cataracts, insulin resistance and diabetes, testicular atrophy with impaired spermatogenesis, and others. Testicular biopsy findings are specific. To our knowledge, this is the first case of male infertility associated with MD in Syria. However, there are no data on the prevalence of myotonic dystrophy type 1 (MD1) in Syria.

Conclusion:
The practicing physician should keep in mind the frequent association between MD and infertility.