bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐cell RNA sequencing reveals the heterogeneity of epithelial cell and fibroblast cells from non‐ to metastatic lymph node OTSCC
Authors: Song Dandan , Yang Fei , Sun Yang , Wu Xingwen , Zhou Qianrong , Bi Wei , Sun Jian , Li Siyi , Yu Youcheng 
Published: January 2024

AbstractLymph node metastasis (LNM) is one of the common features of oral tongue squamous cell carcinoma (OTSCC). LNM is also taken as a sign of advanced OTSCC and poor survival rate. Recently, single‐cell RNA sequencing has been applied in investigating the heterogeneity of tumor microenvironment and discovering the potential biomarkers for helping the diagnosis and prognosticating. Pathogenesis of LNM in OTSCC remains unknown. Specifically, cancer‐associated fibroblasts (CAFs) and epithelial tumor cells could foster the progression of tumors. Thus, in this study, we aimed to comprehensively analyze the roles of subpopulations of CAFs and epithelial tumor cells in lymph node metastatic OTSCC using the integration of OTSCC single‐cell RNA sequencing datasets. Four distinct subtypes of CAFs, namely vascular CAFs, myofibroblast CAFs, inflammatory CAFs, and growth arrest CAFs were successfully discovered in LNM tumor and confirmed the roles of GAS and PTN pathways in the progression of tumor metastasis. In addition, NKAIN2+ epithelial cells and FN1+ epithelial cells specifically exhibited an upregulation of PTN, NRG, MIF, and SPP1 signaling pathways in the metastatic OTSCC. In doing so, we put forth some potential biomarkers that could be utilized for the purpose of diagnosing and prognosticating OTSCC during its metastatic phase and tried to confirm by immunofluorescence assays.
Cortisol as a Marker of Pain and Distress Following Acute Musculoskeletal Trauma
Authors: Jesin Joshua A. , Walton David M. 
Published: January 2024

Objectives:The best available predictors of chronic pain development broadly encompass baseline metrics of cognition (i.e. beliefs/expectations) about the trauma and resulting symptoms. In the context of musculoskeletal trauma we have previously shown the Traumatic Injuries Distress Scale (TIDS) capable of risk stratifying cohorts for chronic pain development. Here we explore whether the physiologic marker cortisol shows meaningful associations with cognitions predictive of pain outcomes.Methods:Data for these cross-sectional analyses were drawn from an observational study that recruited 130 participants presenting to hospital with pain related to a recent non-catastrophic MSK trauma. Cortisol was measured from participant’s hair, saliva, and blood. In addition to pain and distress questionnaires, metadata such as age, sex, BMI, adverse childhood events, pre-trauma stress levels and pre-existing physical/psychological comorbidities were collected.Results:We found no significant associations between cortisol levels and pain or distress in isolation. When stratified by person-level variables, associations were revealed with distress (TIDS) in young age and low pre-trauma stress subgroups (hair cortisol) and low BMI (blood cortisol). Through hierarchical regression analysis we found the ‘cortisol X age’ or ‘cortisol X stress’ interaction terms significantly improved TIDS prediction beyond either variable in isolation (Age: ∆R2=15.1%; Pre-trauma stress: ∆R2=9.1%).Discussion:Our findings suggest that while linear correlations between pain-related distress and cortisol may be overly simplistic, certain person-level variables such as age, pre-trauma stress and BMI are worthy of consideration for experimental design or confounder characterization in future studies of pain and distress following musculoskeletal injuries especially when ‘trait’ (hair) cortisol is the predictor variable.
AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy
Authors: Yin Yichun , Wang Jian , Yi Junxuan , Zhang Kaiyue , Yin Zimeng , Jin Shunzi , Zheng Baisong 
Published: January 2024

Abstract

Background:
Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.

Methods:
The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro. A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8+ T cells in TME were analyzed by flow cytometry.

Results:
Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro. AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1+/CD8+ T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ)+ or Ki67+ CD8 T cells and decreasing the levels of CD8+ Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8+ T cells proliferation, and weakening CD8+ T cells depletion.

Conclusions:
This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8+ T cells in TME.
Targeting HIV persistence in the tissue
Authors: Pieren Daan K.J. , Benítez-Martínez Aleix , Genescà Meritxell 
Published: January 2024

Purpose of review
The complex nature and distribution of the HIV reservoir in tissue of people with HIV remains one of the major obstacles to achieve the elimination of HIV persistence. Challenges include the tissue-specific states of latency and viral persistence, which translates into high levels of reservoir heterogeneity. Moreover, the best strategies to reach and eliminate these reservoirs may differ based on the intrinsic characteristics of the cellular and anatomical reservoir to reach.

Recent findings
While major focus has been undertaken for lymphoid tissues and follicular T helper cells, evidence of viral persistence in HIV and non-HIV antigen-specific CD4+ T cells and macrophages resident in multiple tissues providing long-term protection presents new challenges in the quest for an HIV cure. Considering the microenvironments where these cellular reservoirs persist opens new venues for the delivery of drugs and immunotherapies to target these niches. New tools, such as single-cell RNA sequencing, CRISPR screenings, mRNA technology or tissue organoids are quickly developing and providing detailed information about the complex nature of the tissue reservoirs.

Summary
Targeting persistence in tissue reservoirs represents a complex but essential step towards achieving HIV cure. Combinatorial strategies, particularly during the early phases of infection to impact initial reservoirs, capable of reaching and reactivating multiple long-lived reservoirs in the body may lead the path.
Mosaic Muir Torre Syndrome: Keratoacanthoma as a Piece of the Puzzle
Authors: O'Brien Amber , Macfarlane Sarah , Sommerlad Matthew , Schirwani Schaida 
Published: January 2024

Abstract:
Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.
Evaluating tranexamic acid for the prevention and treatment of obstetric hemorrhage
Authors: Kowalczyk John J. , Cecconi Maurizio , Butwick Alexander J. 
Published: January 2024

Purpose of review
Tranexamic acid (TXA) has emerged as a promising pharmacological adjunct to treat and prevent postpartum hemorrhage (PPH). We provide an overview of TXA, including its pharmacology, key findings of randomized trials and observational studies, and critical patient safety information.

Recent findings
Pharmacokinetic data indicate that TXA infusions result in peak plasma concentration within 3 min (range: 1–6.6 min). Ex-vivo pharmacodynamic data suggest that low-dose TXA (5 mg/kg) inhibits maximum lysis for at least 1 h. In predominantly developing countries, TXA has demonstrated a 19% reduction in the risk of bleeding-related death among patients with PPH. Based on high-quality randomized trials, TXA prophylaxis does not effectively reduce the risk of PPH during vaginal delivery and is likely ineffective in reducing the PPH risk during cesarean delivery. TXA exposure does not increase the risk of maternal thrombotic events. Maternal deaths have occurred from accidental intrathecal TXA injection from look-alike medication errors.

Summary
TXA has shown promise as an important adjunct for PPH treatment, especially in low-resource settings. However, TXA is not recommended as PPH prophylaxis during vaginal or cesarean delivery. Patient safety initiatives should be prioritized to prevent maternal death from accidental intrathecal TXA injection.
Provider Perceived Facilitators and Barriers to Identifying, Perceiving, and Seeking Healthcare for Chronic Pain After TBI: A Qualitative NIDILRR and VA TBI Model Systems Collaborative Project
Authors: Nakase-Richardson Risa , Cotner Bridget A. , Agtarap Stephanie D. , Martin Aaron M. , Ching Deveney , O'Connor Danielle R. , Tweed Amanda , Haun Jolie N. , Hanks Robin A. , Bergquist Thomas F. , Hammond Flora M. , Zafonte Ross D. , Hoffman Jeanne M. 
Published: January 2024

Objective:
Identify determinants to chronic pain healthcare for persons with traumatic brain injury (TBI) informed by an Access to Care Framework. Findings related to the Access Framework's core domains of identifying a need, perceptions of the need, and seeking healthcare are reported.

Setting:
Community.

Participants:
Healthcare providers (n = 63) with 2 or more years of experience treating persons with TBI interviewed between October 2020 and November 2021.

Design:
Descriptive, qualitative study.

Main Measures:
Semi-structured interviews with open-ended questions of chronic pain management for persons with TBI. Informed by the Access Framework, responses were coded by and categorized within the domains of identifying healthcare needs, perceptions of needs, and factors related to healthcare seeking from the supply and demand perspective.

Results:
For the overall sample, 14 facilitators and 6 barriers were endorsed by more than 20% of the provider cohort. Top facilitators included on-site availability of needed resources and treatments (94%), adequate time and provider capability to ensure patient comprehension of diagnosis and treatment plans (83%), and establishing patient motivation and buy-in with the treatment plan (75%). Barriers most endorsed included policies impacting access (46%), wait times for services (41%), and patient uncertainty regarding telehealth commonly due to cognitive and physical challenges (37%). Unique determinants are reported across civilian versus Department of Veterans Affairs (VA) healthcare systems and different provider types.

Conclusion:
This is the first evidence-based study to inform policy and planning to improve access to high-quality chronic pain treatments for persons with TBI. Results will inform future interventions at the systems, patient, and policy levels of healthcare that can be tailored to healthcare settings (VA, Civilian) and types of providers (rehabilitation therapists, psychologists, and medical). Evidence-informed interventions may help minimize healthcare disparities experienced by persons with TBI and facilitate access to high-quality, evidence-informed chronic pain care.
The Interaction of Opiate Misuse and Marijuana Use on Behavioral Health Outcomes Using the Traumatic Brain Injury Model Systems Pain Collaborative Dataset
Authors: Callender Librada , Lai Tony , Driver Simon , Ketchum Jessica M. , Ochoa Christa , Corrigan John D. , Hammond Flora M. , Harrison-Felix Cindy , Martin Aaron M. , Rabinowitz Amanda R. , Starosta Amy J. , Dubiel Randi 
Published: January 2024

Objective:To determine if the interaction of opiate misuse and marijuana use frequency is associated with behavioral health outcomes.Setting:Community.Participants:Three thousand seven hundred fifty participants enrolled in the Traumatic Brain Injury Model Systems who completed the Pain Survey and had complete opioid use and marijuana use information.Design:Cross-sectional, secondary analysis from a multisite observational cohort.Main Outcome Measure(s):Clinically significant behavioral health symptoms for posttraumatic stress disorder (PTSD), depression, anxiety, and sleep quality.Results:Three thousand five hundred thirty-five (94.3%) participants did not misuse opiates, 215 (5.7%) did misuse opiates (taking more opioid pain medication than prescribed and/or using nonprescription opioid pain medication); 2683 (70.5%) participants did not use marijuana, 353 (9.3%) occasionally used marijuana (less than once a week), and 714 (18.8%) regularly used marijuana (once a week or more frequently). There was a statistically significant relationship (P< .05) between the interaction of opiate misuse and marijuana use frequency and all behavioral health outcomes and several covariates (age, sex, cause of injury, severity of injury, and pain group category). Pairwise comparisons confirm that statistically significant associations on behavioral health outcomes are driven by endorsing opiate misuse and/or regular marijuana use, but occasional marijuana use was not associated.Conclusions:Higher odds of clinically significant PTSD, depression, anxiety, and poor sleep quality are present in people with traumatic brain injury (TBI) who misuse opiates and/or who use marijuana regularly. In the absence of opiate misuse, regular marijuana use had higher odds of worse behavioral health outcomes than occasional and no use. The interaction of opiate misuse and regular marijuana use yielded the highest odds. Individuals with TBI should be informed of the relationship of substance use and behavioral health outcomes and that current chronic pain may mediate the association.
Community-acquired bacterial pneumonia in children: an update on antibiotic duration and immunization strategies
Authors: Lyon Edward , Olarte Liset 
Published: January 2024

Purpose of review
This review is structured to update clinicians on the epidemiology, antibiotic treatment, and prevention of pediatric bacterial pneumonia. The review provides information regarding the current research on antibiotic management for bacterial pneumonia and the newest immunization recommendations to prevent pneumococcal pneumonia and other respiratory infections.

Recent findings
The recommended length of antibiotic therapy for bacterial pneumonia has been discrepant between low-income and high-income countries. Recently, randomized controlled trials conducted in high-income countries provided evidence to support a short antibiotic course (3–5 days) for uncomplicated bacterial pneumonia in otherwise healthy children. The negative impact of inaccurate penicillin allergy labels in children with pneumonia has emphasized the importance of prompt allergy de-labeling. Newer pneumococcal vaccines are recommended for children and are expected to have a significant impact on bacterial pneumonia rates.

Summary
Pediatric bacterial pneumonia is an important contributor to childhood morbidity and mortality. A short antibiotic course seems to be sufficient for the outpatient management of uncomplicated bacterial pneumonia; however, more studies are required in the inpatient setting. Future studies will inform the impact of recently introduced pneumococcal and respiratory syncytial virus vaccines on the epidemiology of bacterial pneumonia.
What is in the pipeline for new treatments for bladder pain syndrome/ interstitial cystitis?
Authors: Dias Diogo , Mendes Pedro Abreu , Oliveira Paulo Dinis , Pinto Rui Almeida 
Published: January 2024

Purpose of review
Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years.

Recent findings
During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy.

Summary
Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.
Retroperitoneal Castleman’s disease in a young Nepalese girl: A rare cause of childhood abdominal mass
Authors: Shrestha Ashish Lal , Mishra Aakash , Khadka Sagar , Dhakhwa Ramesh 
Published: January 2024

Introduction:
Castleman’s disease (CD), or benign angio-follicular lymph node hyperplasia, is an uncommon condition in childhood. When a child presents with a huge retroperitoneal mass and inconclusive findings on clinico-radiological evaluation or tissue sampling, management becomes exceedingly difficult. CD herein becomes an uncommon presentation of an uncommon diagnosis.

Case presentation:
A six-year-old girl with no past medical problems presented to the office with a slowly progressive, painless mass over the right lumbar region for a year. Abdominal ultrasound showed a well-defined oval mass in the right periumbilical region, further evaluation of which with a computed tomography scan suggested lymphoma. A preoperative core-cut biopsy could not confirm the findings and suggested a neoplastic lesion, probably an inflammatory myofibroblastic tumour or small round cell tumour. She underwent an exploratory laparotomy with in-toto excision of the mass. Intraoperatively, a solid retroperitoneal tumour measuring 8×8×6 cm was found. Histopathology and immunohistochemistry confirmed a unicentric CD of the hyaline-vascular type. At two years of follow-up, she remained asymptomatic and disease-free.

Conclusion:
While CD in children is rare, retroperitoneal localization of the same can further add to the diagnostic conundrum. However, if carefully considered, an en-bloc surgical resection offers complete treatment.
Takayasu arteritis presenting as a stroke in young: a case report
Authors: Oli Paras , Poudel Prabhat , KC Shradha , Thapa Neeraj , KC Aastha 
Published: January 2024

Introduction:
Takayasu arteritis is a large-vessel vasculitis predominantly seen in young women. Lack of signs and symptoms in the early stage of the disease often delays the diagnosis and thus leads to significant morbidity and mortality. One severe complication that may arise is a significant narrowing of blood vessels, potentially leading to life-threatening ischemic repercussions.

Case presentation:
The authors present a case of a 29-year-old female who presented to our ER with features of left-sided hemiparesis and right-sided facial deviation. Computed tomography angiography and Carotid Doppler helped in making the diagnosis of Takayasu arteritis. She was managed with prednisolone and mycophenolate mofetil. She has been on a regular follow-up for the last year and is currently stable.

Conclusion:
Even being a rare scenario, stroke can be the initial presentation of Takayasu arteritis. Early diagnosis and management in young patients are vital in keeping the disease at bay and preventing physical, mental, and socio-economic adversities.
Management of recurrent lumbar disc herniation: a comparative analysis of posterior lumbar interbody fusion and repeat discectomy
Authors: Musa Gerald , Makirov Serik K. , Chmutin Gennady E. , Susin Sergey V. , Kim Alexander V. , Antonov Gennady I. , Otarov Olzhas , Ndandja Dimitri T.K. , Egor G Chmutin , Chaurasia Bipin 
Published: January 2024

Background:
For recurrent lumbar disc herniation, many experts suggest a repeat discectomy without stabilization due to its minimal tissue manipulation, lower blood loss, shorter hospital stay, and lower cost, recent research on the role of instability in disc herniation has made fusion techniques popular among spinal surgeons. The authors compare the postoperative outcomes of posterior lumbar interbody fusion (PLIF) and repeat discectomy for same-level recurrent disc herniation.

Methods:
The patients included had previously undergone discectomy and presented with a same-level recurrent lumbar disc herniation. The patients were placed into two groups: 1) discectomy only, 2) PLIF based on the absence or presence of segmental instability. Preoperative and postoperative Oswestry disability index scores, duration of surgery, blood loss, duration of hospitalization, and complications were analyzed.

Results:
The repeat discectomy and fusion groups had 40 and 34 patients, respectively. The patients were followed up for 2.68 (1–4) years. There was no difference in the duration of hospitalization (3.73 vs. 3.29 days P=0.581) and operative time (101.25 vs. 108.82 mins, P=0.48). Repeat discectomy had lower intraoperative blood loss, 88.75 ml (50–150) versus 111.47 ml (30–250) in PLIF (P=0.289). PLIF had better ODI pain score 4.21 (0–10) versus 9.27 (0–20) (P-value of 0.018). Recurrence was 22.5% in repeat discectomy versus 0 in PLIF.

Conclusion:
PLIF and repeat discectomy for recurrent lumbar disc herniation have comparable intraoperative blood loss, duration of surgery, and hospital stay. PLIF is associated with lower durotomy rates and better long-term pain control than discectomy. This is due to recurrence and progression of degenerative process in discectomy patients, which are eliminated and slowed, respectively, by PLIF.